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J. Biol. Chem., Vol. 279, Issue 4, 2438-2452, January 23, 2004
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From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
Probing of the mouse EST data base at GenBankTM with known tryptase cDNAs resulted in the identification of undiscovered serine protease transcripts whose genes reside at a 1.5-Mb complex on mouse chromosome 17A3.3. Mouse tryptase-5 (mT5), tryptase-6 (mT6), and mast cell protease-11 (mMCP-11) are new members of this serine protease superfamily whose amino acid sequences are 3654% identical to each other and to their other 10 family members. The 13 functional mouse proteases can be subdivided into two subgroups based on conserved features in their propeptides. Of the three new serine proteases, mT6 is most widely expressed in tissues. mT5 is preferentially expressed in smooth muscle, whereas mMCP-11 is preferentially expressed in the spleen and bone marrow. In contrast to mT5 and mT6, mMCP-11 is also expressed in mast cells. Although mT6 and mMCP-11 are constitutively secreted when expressed in mammalian and insect cells, mT5 remains membrane-associated. The fact that recombinant mT5, mT6, and mMCP-11 possess non-identical expression patterns and substrate specificities suggests that each protease has a unique function in vivo. Of the 13 functional mouse tryptase genes identified at the complex, 12 have orthologs that reside in the syntenic region of human chromosome 16p13.3. The establishment of these ortholog pairs helps clarify the evolutionary relationship of the serine protease locus in the two species. This information provides a useful framework for the functional analysis of each protease using gene targeting and other molecular approaches.
Received for publication, July 28, 2003 , and in revised form, October 15, 2003.
* This work was supported in part by Grants HL-36110 and HL-63284 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AAP23216
Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
Both authors contributed equally to this work.
¶ To whom correspondence should be addressed: Dept. of Medicine, Brigham and Women's Hospital, Smith Bldg., Rm. 616B, 1 Jimmy Fund Way, Boston, MA 02115. Tel.: 617-525-1231; Fax: 617-525-1310; E-mail: rstevens{at}rics.bwh.harvard.edu.
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