Metalloproteinase ADAM 22

#1. Field of the Invention

#The present invention relates to a novel metalloproteinase. More specifically, isolated nucleic acid molecules are provided encoding a human protein named ADAM 22. ADAM 22 polypeptides are also provided, as are vectors, host cells, antibodies directed to ADAM 22 polypeptides, and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of the enzyme's activity. Also provided are diagnostic and therapeutic methods for detecting and treating diseases, disorders or conditions that involve the enzyme, and therapeutic methods for treating, preventing, and/or diagnosing such diseases, disorders, and/or conditions.

#2. Related Art

#FIGS. 1A-1D show the nucleotide sequence (SEQ ID NO:1) and deduced amino acid (SEQ ID NO:2) sequence of the ADAM 22 protein of the invention. The protein has a leader sequence of about 27 amino acid residues (underlined). It is further predicted that amino acid residues from about 28 to about 690 constititute the extracellular domain, that amino acid residues from about 691 to about 707, or alternatively from about Gly 680 to about Leu 716 constitute the transmembrane domain, and that amino acid residues from about 708 to about 790, or alternatively from about Lys 717 to about Lys 790 constitute the intracellular domain.

#FIGS. 2A-2C show the regions of similarity between the amino acid sequences of the ADAM 22 polypeptide and human ADAM 20 polypeptide (SEQ ID NO:3). Identical amino acids between the two polypeptides are shaded, while conservative amino acid are boxed. By examining the regions of amino acids shaded and/or boxed, the skilled artisan can readily identify conserved domains between the two polypeptides. These conserved domains are preferred embodiments of the present invention.

#FIG. 3 shows an analysis of the ADAM 22 amino acid sequence. Alpha, beta, turn and coil regions; hydrophilicity and hydrophobicity; amphipathic regions; flexible regions; antigenic index and surface probability are shown, and all were generated using the default settings. In the “Antigenic Index or Jameson-Wolf” graph, the positive peaks indicate locations of the highly antigenic regions of the ADAM 22 protein, i.e., regions from which epitope-bearing peptides of the invention can be obtained. The domains defined by these graphs are contemplated by the present invention.

#The data presented in FIG. 3 are also represented in tabular form in Table I. The columns are labeled with the headings “Res”, “Position”, and Roman Numerals I-XIV. The column headings refer to the following features of the amino acid sequence presented in FIG. 3, and Table I: “Res”: amino acid residue of SEQ ID NO:2 and FIGS. 1A-1D; “Position”: position of the corresponding residue within SEQ ID NO:2 and FIGS. 1A-1D; I: Alpha, Regions—Garnier-Robson; II: Alpha, Regions—Chou-Fasman; III: Beta, Regions—Garnier-Robson; IV: Beta, Regions—Chou-Fasman; V: Turn, Regions—Garnier-Robson; VI: Turn, Regions—Chou-Fasman; VII: Coil, Regions—Garnier-Robson; VIII: Hydrophilicity Plot—Kyte-Doolittle; IX: Hydrophobicity Plot—Hopp-Woods; X: Alpha, Amphipathic Regions—Eisenberg; XI: Beta, Amphipathic Regions—Eisenberg; XII: Flexible Regions—Karplus-Schulz; XIII: Antigenic Index—Jameson-Wolf; and XIV: Surface Probability Plot—Emini.

#The present invention provides isolated nucleic acid molecules comprising a polynucleotide encoding an ADAM 22 polypeptide having the amino acid sequence shown in SEQ ID NO:2, which was determined by sequencing cloned cDNA.

#The ADAM 22 protein of the present invention shares sequence homology with ADAM 20, Genbank Accession No. AF029899 (FIG. 2) (SEQ ID NO:3). The nucleotide sequence shown in SEQ ID NO:1 was obtained by sequencing a human cDNA contained in clone “HTEMZ33”, which was deposited as plasmid DNA on Jan. 13, 2000 at the American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, and given accession number _____. The deposited cDNA is inserted in the pBluescript SK(−) plasmid (Stratagene, LaJolla, Calif.).