Polynucleotides encoding human ion-exchanger proteins

Details Polynucleotides encoding human ion-exchanger proteins Polynucleotides encoding human ion-exchanger proteins

2001-09-24

2004-09-07

Kunz, Gary (Department: 1646)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C435S320100, C435S252300, C435S254110, C435S254200, C536S023500

Reexamination Certificate

active

06787352

ABSTRACT:

1. INTRODUCTION
The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins that share sequence similarity with mammalian membrane proteins. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or over express the disclosed genes, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed genes that can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, and cosmetic or nutriceutical applications.
2. BACKGROUND OF THE INVENTION
Membrane proteins can serve as recognition markers, mediate signal transduction, and can mediate or facilitate the passage of materials across the lipid bilayer. As such, membrane proteins, are proven drug targets.
3. SUMMARY OF THE INVENTION
The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with mammalian sodium-calcium exchanger proteins, sodium-calcium potassium exchanger proteins, and potassium dependent versions of the same.
The novel human nucleic acid sequences described herein encode alternative proteins/open reading frames (ORFs) of 603, 316 and 353 amino acids in length (SEQ ID NOS: 2, 4, and 6).
The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPs, or portions thereof, that compete with native NHP, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and open reading frame or regulatory sequence replacement constructs) or to enhance the expression of the described NHPs (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHP sequence, or “knock-outs” (which can be conditional) that do not express a functional NHP. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cells (“ES cells”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHPs. When the unique NHP sequences described in SEQ ID NOS:1-7 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene as well as a method of assigning function to previously unknown genes. In addition, animals in which the unique NHP sequences described in SEQ ID NOS:1-7 are “knocked-out” provide a unique source in which to elicit antibodies to homologous and orthologous proteins that would have been previously viewed by the immune system as “self” and therefore would have failed to elicit significant antibody responses. To these ends, gene trapped knockout ES cells have been generated in murine homologs of the described NHPs.
Additionally, the unique NHP sequences described in SEQ ID NOS:1-7 are useful for the identification of protein coding sequence and mapping a unique gene to a particular chromosome. These sequences identify actual, biologically relevant, exon splice junctions as opposed to those that might have been predicted bioinformatically from genomic sequence alone. The sequences of the present invention are also useful as additional DNA markers for restriction fragment length polymorphism (RFLP) analysis, and in forensic biology.
Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.
4. DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES
The Sequence Listing provides the sequences of the NHP ORFs encoding the described NHP amino acid sequences. SEQ ID NO:7 describes a polynucleotide encoding a NHP ORF with regions of flanking sequence.


REFERENCES:
patent: 4215051 (1980-07-01), Schroeder et al.
patent: 4376110 (1983-03-01), David et al.
patent: 4594595 (1986-06-01), Struckman
patent: 4631211 (1986-12-01), Houghten
patent: 4689405 (1987-08-01), Frank et al.
patent: 4713326 (1987-12-01), Dattagupta et al.
patent: 4873191 (1989-10-01), Wagner et al.
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5252743 (1993-10-01), Barrett et al.
patent: 5272057 (1993-12-01), Smulson et al.
patent: 5424186 (1995-06-01), Fodor et al.
patent: 5445934 (1995-08-01), Fodor et al.
patent: 5459127 (1995-10-01), Felgner et al.
patent: 5556752 (1996-09-01), Lockhart et al.
patent: 5700637 (1997-12-01), Southern
patent: 5744305 (1998-04-01), Fodor et al.
patent: 5830721 (1998-11-01), Stemmer et al.
patent: 5837458 (1998-11-01), Minshull et al.
patent: 5869336 (1999-02-01), Meyer et al.
patent: 5877397 (1999-03-01), Lonberg et al.
patent: 5948767 (1999-09-01), Scheule et al.
patent: 6075181 (2000-06-01), Kucherlapati et al.
patent: 6110490 (2000-08-01), Thierry
patent: 6150584 (2000-11-01), Kucherlapati et al.
Li, X.-F. et al, Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4. J. Biol. Chem. 277:48410-48417, 2002.*
Lytton et al, K+-dependent Na+/Ca2+ exchangers in the brain. Ann. N. Y. Acad. Sci. 976:382-393, 2002.*
Li, X-F. et al, GenBank, Accession No. AF52075, Jul. 7, 2002.*
Bird et al, 1988, “Single-Chain Antigen-Binding Proteins”, Science 242:423-426.
Bitter et al, 1987, “Expression and Secretion Vectors for Yeast”, Methods in Enzymology 153:516-544.
Colbere-Garapin et al, 1981, “A New Dominant Hybrid Selective Marker for Higher Eukaryotic Cells”, J. Mol. Biol. 150:1-14.
Gautier et al, 1987, “&agr;-DNA IV:&agr;-anomeric and &bgr;-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physiochemical properties and poly (rA) binding”, Nucleic Acids Research 15(16):6625-6641.
Gordon, 1989, “Transgenic Animals”, International Review of Cytology, 115:171-229.
Greenspan et al, 1993, “Idiotypes: structure and immunogenicity”, FASEB Journal 7:437-444.
Gu et al, 1994, “Deletion of a DNA Polymerase &bgr; Gene Segment in T Cells Using Cell Type-Specific Gene Targeting”, Science 265:103-106.
Huse et al, 1989, “Generation of a Large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda”, Science 246:1275-1281.
Huston et al, 1988, “Protein engineering of antibody binding sites Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced inEscherichia coli”, Proc Natl. Acad. Sci USA 85:5879-5883.
Inoue et al, 1987, “Sequence-dependent hydrolysis of RNA using modified oligonucleotide splints and R Nase H”, FEBS Letters 215(2):327-330.
Inoue et al, 1987, “Synthesis and hybridization studies on two complementary nona(2′-O-methyl)ribonucleotides”, Nucleic Acids Research 15(15):6131-6149.
Inouye & Inouye, 1985, “Up-promoter mutations in the Ipp gene ofEscherichia coli”, Nucleic Acids Research 13(9)3101-3110.
Janknecht et al, 1991, “Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus”, PNAS 88:8972-8976.
Kohler & Milstein, 1975, “Continuous cultures of fused cells secreting antibody of predefined specificity”, Nature 256:495-497.
Lasko et al, 1992, “Targeted oncogene activation by site-specific recombination in transgenic mice”, Proc. Natl. Acad. Sci. USA 89:6232-6236.
Lavitrano et al, 1989, “Sperm Cells as Vectors for Introducing Foreign DNA into Eggs: Genetic Transformation of Mice”, Ce

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