Structure and Expression of the Human MEP1A Gene Encoding the α Subunit of Metalloendopeptidase Meprin A

Jiang, Weiping; Le, Brian

doi:10.1006/abbi.2000.1873

Cited by 14 publications

(6 citation statements)

References 33 publications

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“…Both of these turned out to be known lineage-specific genes of gastrointestinal epithelia (Jiang and Le, 2000;Williams et al, 2001) and these data were independently confirmed by our own experimental RT-PCR data (Fig. 2b).…”

Section: Expression Profiling Of Candidate Genes In Human Tissuessupporting

confidence: 83%

In silico strategy for detection of target candidates for antibody therapy of solid tumors

Helftenbein¹,

Koslowski²,

Dhaene³

et al. 2008

Gene

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Section: Expression Profiling Of Candidate Genes In Human Tissuessupporting

confidence: 83%

In silico strategy for detection of target candidates for antibody therapy of solid tumors

Helftenbein¹,

Koslowski²,

Dhaene³

et al. 2008

Gene

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“…Japanese investigators have reported the purification of meprin from human kidney and have assigned to it a major role in the degradation of parathyroid hormone (Yamaguchi, Fukase et al 1994). Although meprin α mRNA has been detected in different human tissues including kidney in an immunoblot (Jiang and Le 2000) the subunit was not detected in human kidneys of causasian origin in other studies (ES, unpublished data). It is not inconceivable that different human meprin expression phenotypes may exist among the world population.…”

Section: Meprinsmentioning

confidence: 83%

Meprins, membrane-bound and secreted astacin metalloproteinases

Sterchi

Stöcker

Bond

2008

Molecular Aspects of Medicine

177

183

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The astacins are a subfamily of the metzincin superfamily of metalloproteinases. The first to be characterized was the crayfish enzyme astacin. To date more than 200 members of this family have been identified in species ranging from bacteria to humans. Astacins are involved in developmental morphogenesis, matrix assembly, tissue differentiation and digestion. Family members include the procollagen C-proteinase (BMP1, bone morphogenetic protein 1), tolloid and mammalian tolloidlike, HMP (Hydra vulgaris metalloproteinase), sea urchin BP10 (blastula protein) and SPAN (Strongylocentrotus purpuratus astacin), the 'hatching' subfamily comprising alveolin, ovastacin, LCE, HCE ('low' and 'high' choriolytic enzymes), nephrosin (from carp head kidney), UVS.2 from frog, and the meprins. In the human and mouse genomes, there are six astacin family genes (two meprins, three BMP1/tolloid-like, one ovastacin), but in Caenorhabditis elegans there are 40.Meprins are the only astacin proteinases that function on the membrane and extracellularly by virtue of the fact that they can be membrane-bound or secreted. They are unique in their domain structure and covalent subunit dimerization, oligomerization propensities, and expression patterns. They are normally highly regulated at the transcriptional and post-translational levels, localize to specific membranes or extracellular spaces, and can hydrolyse biologically active peptides, cytokines, extracellular matrix (ECM) proteins and cell-surface proteins. The in vivo substrates of meprins are unknown, but the abundant expression of these proteinases in the epithelial cells of the intestine, kidney and skin provide clues to their functions.

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“…The meprin ␣ and ␤ subunits are expressed early in embryonic development of mouse kidney and intestine, by day 11, and have different patterns of expression in the suckling phase and after weaning (4). Homologous enzymes are found in rat and human kidney and intestine (1,5,6). Meprins are also expressed in leukocytes of intestinal lamina propria and in cancer cells and are consequently implicated in inflammation and cancer growth and metastasis (7,8).…”

mentioning

confidence: 99%

Marked Differences between Metalloproteases Meprin A and B in Substrate and Peptide Bond Specificity

Bertenshaw¹,

Turk²,

Hubbard³

et al. 2001

Journal of Biological Chemistry

105

112

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Meprin A and B are highly regulated, secreted, and cell-surface metalloendopeptidases that are abundantly expressed in the kidney and intestine. Meprin oligomers consist of evolutionarily related ␣ and/or ␤ subunits. The work herein was carried out to identify bioactive peptides and proteins that are susceptible to hydrolysis by mouse meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide fragment 14 -27 and gastrin 17, regulatory molecules of the gastrointestinal tract, were found to be the best peptide substrates for meprin A and B, respectively. Peptide libraries and a variety of naturally occurring peptides revealed that the meprin ␤ subunit has a clear preference for acidic amino acids in the P1 and P1 sites of substrates. The meprin ␣ subunit selected for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues in the P1 and P1 sites, and proline was the most preferred amino acid at the P2 position. Thus, although the meprin ␣ and ␤ subunits share 55% amino acid identity within the protease domain and are normally localized at the same tissue cell surfaces, they have very different substrate and peptide bond specificities indicating different functions. Homology models of the mouse meprin ␣ and ␤ protease domains, based on the astacin crystal structure, revealed active site differences that can account for the marked differences in substrate specificity of the two subunits.Meprin A and B are zinc metalloendopeptidases composed of evolutionarily related ␣ and/or ␤ subunits. They are members of the astacin family and are highly expressed in brush border membranes of the intestine and renal proximal tubules (1, 2). Meprins are particularly abundant in mouse juxtamedullary nephrons and constitute ϳ5% of total protein in renal brush border membranes (3). The meprin ␣ and ␤ subunits are expressed early in embryonic development of mouse kidney and intestine, by day 11, and have different patterns of expression in the suckling phase and after weaning (4). Homologous enzymes are found in rat and human kidney and intestine (1,5,6). Meprins are also expressed in leukocytes of intestinal lamina propria and in cancer cells and are consequently implicated in inflammation and cancer growth and metastasis (7,8).Mouse kidney meprin A (EC 3.4.24.18) is a homooligomer of ␣ subunits, or a heterooligomer of ␣ and ␤ subunits (2, 9). Mouse kidney meprin B (EC 3.4.24.63) is a homooligomer of ␤ subunits (10). The multidomain ␣ and ␤ meprin subunits are highly glycosylated and form disulfide-linked dimers and higher order oligomers by noncovalent interactions (11,12). Meprins containing at least one ␤ subunit remain membranebound by virtue of a transmembrane domain located near the carboxyl terminus of ␤ subunits (1). Mature meprin ␣ homooligomers contain no transmembrane domain and are found in mouse urine (13). The expression of the meprin ␣ subunits in mice is strain-dependent (1). Random-bred mice (such as ICR) and many inbred strains of mice (e.g. C57BL/6) express both meprin ␣ and ␤ in...

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Structure and Expression of the Human MEP1A Gene Encoding the α Subunit of Metalloendopeptidase Meprin A

Cited by 14 publications

References 33 publications

In silico strategy for detection of target candidates for antibody therapy of solid tumors

In silico strategy for detection of target candidates for antibody therapy of solid tumors

Meprins, membrane-bound and secreted astacin metalloproteinases

Marked Differences between Metalloproteases Meprin A and B in Substrate and Peptide Bond Specificity

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