Novel nucleic acid sequences encoding adenylate kinase, phospholipid scramblase-like, DNA fragmentation factor-like, phosphatidylserine synthase-like, and ATPase-like molecules and uses therefor

• US 20030092116A1
• Filed: 06/07/2002
• Published: 05/15/2003
• Est. Priority Date: 02/10/2000
• Status: Active Grant

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Kapeller-Libermann, Rosana, Meyers, Rachel E., Chun, Miyoung, Glucksmann, Maria Alexandra
• Granted Patent: US 6,953,682 B2
• Time in Patent Office: Days
• US Class Current: 435/69.1
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12N 9/1229 Phosphotransferases with a phosphate group as acceptor (2.7.4)
• CPC Class Codes: C12N 9/1288 Transferases for other substituted phosphate groups (2.7.8)
• CPC Class Codes: C12N 9/14 Hydrolases (3)
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention provides isolated nucleic acids molecules that encode novel polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a sequence of the invention has been introduced or disrupted. The invention still further provides isolated proteins, fusion proteins, antigenic peptides and antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Claims

1. An isolated nucleic acid molecule selected from the group consisting of:

a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______;

b) a nucleic acid molecule comprising a fragment of at least 300 nucleotides of the nucleotide sequence of SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______;

c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17 or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______;

d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 6, 11, 17, 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______; and

e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23 under stringent conditions.

2. The isolated nucleic acid molecule of claim 1, which is selected from the group consisting of:

a) a nucleic acid comprising the nucleotide sequence of SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______; and

b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______.

3. The nucleic acid molecule of claim 1 further comprising vector nucleic acid sequences.

4. The nucleic acid molecule of claim 1 further comprising nucleic acid sequences encoding a heterologous polypeptide.

5. A host cell which contains the nucleic acid molecule of claim 1.

6. The host cell of claim 5 which is a mammalian host cell.

7. A non-human mammalian host cell containing the nucleic acid molecule of claim 1.

12. A method for producing a polypeptide selected from the group consisting of:

a) a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______;

b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______; and

c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23;

comprising culturing the host cell of claim 5 under conditions in which the nucleic acid molecule is expressed.

16. A method for detecting the presence of a nucleic acid molecule of claim 1 in a sample, comprising the steps of:

a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and

b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.

17. The method of claim 16, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.

18. A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of claim 1 and instructions for use.

8. An isolated polypeptide selected from the group consisting of:

a) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, or a complement thereof;

b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO;

1, 3, 5, 7, 10, 12, 16, 18, 21, or 23, or a complement thereof under stringent conditions; and

c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO;

2, 6, 11, 17, or 22, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number ______, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO;

2, 6, 11, 17, or 22.

9. The isolated polypeptide of claim 8 comprising the amino acid sequence of SEQ ID NO:

2, 6, 11, 17, 22.

10. The polypeptide of claim 8 further comprising heterologous amino acid sequences.

11. An antibody which selectively binds to a polypeptide of claim 8.

13. A method for detecting the presence of a polypeptide of claim 8 in a sample, comprising:

a) contacting the sample with a compound which selectively binds to a polypeptide of claim 8;

and

b) determining whether the compound binds to the polypeptide in the sample.

14. The method of claim 13, wherein the compound which binds to the polypeptide is an antibody.

15. A kit comprising a compound which selectively binds to a polypeptide of claim 8 and instructions for use.

19. A method for identifying a compound which binds to a polypeptide of claim 8 comprising the steps of:

a) contacting a polypeptide, or a cell expressing a polypeptide of claim 8 with a test compound; and

b) determining whether the polypeptide binds to the test compound.

20. The method of claim 19, wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of:

a) detection of binding by direct detecting of test compound/polypeptide binding; and

,

b) detection of binding using a competition binding assay.

21. A method for modulating the activity of a polypeptide of claim 8 comprising contacting a polypeptide or a cell expressing a polypeptide of claim 8 with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.

22. A method for identifying a compound which modulates the activity of a polypeptide of claim 8, comprising:

a) contacting a polypeptide of claim 8 with a test compound; and

b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.