MEP1A explained

Meprin A subunit alpha also known as endopeptidase-2 or PABA peptide hydrolase is the alpha subunit of the meprin A enzyme that in humans is encoded by the MEP1A gene.^{[1] [2]} The MEP1A locus is on chromosome 6p in humans and on chromosome 17 in mice.^[3]

Function

The meprin alpha subunit product of the MEP1A gene is processed in the endoplasmic reticulum during intracellular transport, and is secreted as homomeric meprin A. Meprin alpha subunits may self-associate, and once secreted, form very large multimers, with a molecular mass of over 1 million daltons. In cells concurrently expressing MEP1B, the meprin alpha and meprin beta subunits form disulfide dimers that interact to form membrane bound heterotetrameric meprin A.

Further reading

• Dumermuth E, Sterchi EE, Jiang WP, etal . The astacin family of metalloendopeptidases . J. Biol. Chem. . 266 . 32 . 21381–5 . 1991 . 10.1016/S0021-9258(18)54648-2 . 1939172 . free .
• Kärgel HJ, Dettmer R, Etzold G, etal . Action of rat liver cathepsin L on glucagon . Acta Biol. Med. Ger. . 40 . 9 . 1139–43 . 1982 . 7340337 .
• Kaushal GP, Walker PD, Shah SV . An old enzyme with a new function: purification and characterization of a distinct matrix-degrading metalloproteinase in rat kidney cortex and its identification as meprin . J. Cell Biol. . 126 . 5 . 1319–27 . 1994 . 8063866 . 10.1083/jcb.126.5.1319 . 2120165 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Dumermuth E, Eldering JA, Grünberg J, etal . Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human small intestine and its expression in COS-1 cells . FEBS Lett. . 335 . 3 . 367–75 . 1994 . 8262185 . 10.1016/0014-5793(93)80421-P . 32599035 . free .
• Bankus JM, Bond JS . Expression and distribution of meprin protease subunits in mouse intestine . Arch. Biochem. Biophys. . 331 . 1 . 87–94 . 1996 . 8660687 . 10.1006/abbi.1996.0286 .
• Chevallier S, Ahn J, Boileau G, Crine P . Identification of the cysteine residues implicated in the formation of alpha 2 and alpha/beta dimers of rat meprin . Biochem. J. . 317 . Pt 3. 731–8 . 1996 . 8760356 . 10.1042/bj3170731. 1217546 .
• Eldering JA, Grünberg J, Hahn D, etal . Polarised expression of human intestinal N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (human meprin) alpha and beta subunits in Madin-Darby canine kidney cells . Eur. J. Biochem. . 247 . 3 . 920–32 . 1997 . 9288916 . 10.1111/j.1432-1033.1997.00920.x . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Lottaz D, Hahn D, Müller S, etal . Secretion of human meprin from intestinal epithelial cells depends on differential expression of the alpha and beta subunits . Eur. J. Biochem. . 259 . 1–2 . 496–504 . 1999 . 9914532 . 10.1046/j.1432-1327.1999.00071.x . free .
• Richter R, Schulz-Knappe P, Schrader M, etal . Composition of the peptide fraction in human blood plasma: database of circulating human peptides . J. Chromatogr. B . 726 . 1–2 . 25–35 . 1999 . 10348167 . 10.1016/S0378-4347(99)00012-2 .
• Köhler D, Kruse M, Stöcker W, Sterchi EE . Heterologously overexpressed, affinity-purified human meprin alpha is functionally active and cleaves components of the basement membrane in vitro . FEBS Lett. . 465 . 1 . 2–7 . 2000 . 10620696 . 10.1016/S0014-5793(99)01712-3 . 22895580 .
• Jiang W, Le B . Structure and expression of the human MEP1A gene encoding the alpha subunit of metalloendopeptidase meprin A . Arch. Biochem. Biophys. . 379 . 2 . 183–7 . 2000 . 10898933 . 10.1006/abbi.2000.1873 .
• Kumar JM, Bond JS . Developmental expression of meprin metalloprotease subunits in ICR and C3H/He mouse kidney and intestine in the embryo, postnatally and after weaning . Biochim. Biophys. Acta . 1518 . 1–2 . 106–14 . 2001 . 11267665 . 10.1016/S0167-4781(01)00188-9.
• Bertenshaw GP, Turk BE, Hubbard SJ, etal . Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity . J. Biol. Chem. . 276 . 16 . 13248–55 . 2001 . 11278902 . 10.1074/jbc.M011414200 . free .
• Ishmael FT, Norcum MT, Benkovic SJ, Bond JS . Multimeric structure of the secreted meprin A metalloproteinase and characterization of the functional protomer . J. Biol. Chem. . 276 . 25 . 23207–11 . 2001 . 11301339 . 10.1074/jbc.M102654200 . free .
• Rösmann S, Hahn D, Lottaz D, etal . Activation of human meprin-alpha in a cell culture model of colorectal cancer is triggered by the plasminogen-activating system . J. Biol. Chem. . 277 . 43 . 40650–8 . 2002 . 12189145 . 10.1074/jbc.M206203200 . free .
• Norman LP, Jiang W, Han X, etal . Targeted Disruption of the Meprin β Gene in Mice Leads to Underrepresentation of Knockout Mice and Changes in Renal Gene Expression Profiles . Mol. Cell. Biol. . 23 . 4 . 1221–30 . 2003 . 12556482 . 10.1128/MCB.23.4.1221-1230.2003 . 141138 .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .

Notes and References

1. Bond JS, Rojas K, Overhauser J, Zoghbi HY, Jiang W . The structural genes, MEP1A and MEP1B, for the alpha and beta subunits of the metalloendopeptidase meprin map to human chromosomes 6p and 18q, respectively . Genomics . 25 . 1 . 300–3 . Jul 1995 . 7774936 . 10.1016/0888-7543(95)80142-9 .
2. Web site: Entrez Gene: MEP1A meprin A, alpha (PABA peptide hydrolase).
3. Banerjee S, Oneda B, Yap LM, Jewell DP, Matters GL, Fitzpatrick LR, Seibold F, Sterchi EE, Ahmad T, Lottaz D, Bond JS . MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease . Mucosal Immunol . 2 . 3 . 220–31 . May 2009 . 19262505 . 2670347 . 10.1038/mi.2009.3 .