Isolated nucleic acid molecules encoding human...

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease

Reexamination Certificate

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C435S320100, C435S252300, C435S254110, C435S325000, C435S419000, C536S023100, C536S023200, C536S023500

Reexamination Certificate

active

06664084

ABSTRACT:

FIELD OF THE INVENTION
The present invention is in the field of enzyme proteins that are related to the transferase enzyme subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.
BACKGROUND OF THE INVENTION
Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the transferase subfamily.
Transferases
The novel human protein, and encoding gene, provided by the present invention shows the greatest degree of similarity to a glucuronyltransferase cloned from a rat brain cDNA library (Seiki et al.,
Biochem. Biophys. Res. Commun.
255 (1), 182-187 (1999)). This glucuronyltransferase is important for the biosynthesis of the HNK-1 carbohydrate epitope of glycoproteins. It was demonstrated that transfection of glucuronyltransferase cDNA into COS-1 cells caused the HNK-1 carbohydrate epitope to be expressed on the cell surfaces and also caused the cells to undergo morphological changes. The rat glucuronyltransferase has type II transmembrane topology and the amino acid sequence shares 49% identity with rat GlcAT-P, which is another glucuronyltransferase involved in HNK-1 biosynthesis (Seiki et al.,
Biochem. Biophys. Res. Commun.
255 (1), 182-187 (1999); for information on GlcAT-P, see Terayama et al. (1997) Proc. Natl. Acad. Sci. USA 94, 6093-6098).
Enzyme proteins, particularly members of the transferase enzyme subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the transferase enzyme subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.
SUMMARY OF THE INVENTION
The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the transferase enzyme subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in
FIG. 1
indicates expression in humans in testis, prostate, kidney, brain (including fetal brain), ear, and lung.


REFERENCES:
patent: WO 0075298 (2000-12-01), None
patent: WO 0159063 (2001-08-01), None
Marcos et al. Homo spaiens UDP-glucuronyltransferase-S (GLCATS) mRNA, complete cds. GenBank Accession No. AY070019. Published Jan. 7, 2002.*
Seiki et al. Molecular Cloning and Expression of a Second Glucuronyltransferase Involved in the Biosynthesis of the HNK-1 Carbohydrate Epitope. Biochemical and Biophysical Research Communications (1999) 255:182-187.*
Hillier et al. zt98d09.r1 Soares testis_NHT Homo sapiens cDNA clone. GenBank Accession No. AA421030. Published Oct. 16, 1997.*
Shimoda Yasushi et al. “Cloning and Expression of a Novel Galactoside Betal, 3-Glucuronyltransferase Involved in the Biosynthesis of HNK-1 Epitope.” Journal of Biological Chemistry. vol. 274, No. 24, Jun. 11, 1999, pp. 17115-17122.
Tracey, A. Database EMBL 'Online! Nov. 22, 2000, Accession No. AL450320.
Birren B. et al. Database EMBL 'Online! “Homo Sapiens Chromosome 6, Clone RP11-156I14.” May 10, 2002. Accession No. AC068738.
Tracey A. Database SWALL 'Online! “Galactosylgalactosylxylosylprotein 3-Beta-Glucuronosyltransferase 2.” Oct. 16, 2001. Accession No. Q9NPZ5.

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