MEP1A

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.[5][6] The MEP1A locus is on chromosome 6p in humans and on chromosome 17 in mice.[7]

MEP1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IAF
Identifiers
Aliases	MEP1A, PPHA, meprin A subunit alpha
External IDs	OMIM: 600388 MGI: 96963 HomoloGene: 31323 GeneCards: MEP1A
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p12.3 Start 46,793,389 bp[1] End 46,839,782 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B3|17 19.73 cM Start 43,474,324 bp[2] End 43,502,812 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • zinc ion binding • peptidase activity • metalloendopeptidase activity • GO:0001948 protein binding • hydrolase activity • metallopeptidase activity • metal ion binding Cellular component • integral component of membrane • meprin A complex • integral component of plasma membrane • extracellular exosome • membrane • extracellular Biological process • digestion • proteolysis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4224	17287
Ensembl	ENSG00000112818	ENSMUSG00000023914
UniProt	Q16819	P28825
RefSeq (mRNA)	NM_005588	NM_008585
RefSeq (protein)	NP_005579	NP_032611
Location (UCSC)	Chr 6: 46.79 – 46.84 Mb	Chr 17: 43.47 – 43.5 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.

References

1. GRCh38: Ensembl release 89: ENSG00000112818 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000023914 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bond JS, Rojas K, Overhauser J, Zoghbi HY, Jiang W (Jul 1995). "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. doi:10.1016/0888-7543(95)80142-9. PMID 7774936.
6. "Entrez Gene: MEP1A meprin A, alpha (PABA peptide hydrolase)".
7. Banerjee S, Oneda B, Yap LM, Jewell DP, Matters GL, Fitzpatrick LR, Seibold F, Sterchi EE, Ahmad T, Lottaz D, Bond JS (May 2009). "MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease". Mucosal Immunol. 2 (3): 220–31. doi:10.1038/mi.2009.3. PMC 2670347. PMID 19262505.

Further reading

• Dumermuth E, Sterchi EE, Jiang WP, et al. (1991). "The astacin family of metalloendopeptidases". J. Biol. Chem. 266 (32): 21381–5. PMID 1939172.
• Kärgel HJ, Dettmer R, Etzold G, et al. (1982). "Action of rat liver cathepsin L on glucagon". Acta Biol. Med. Ger. 40 (9): 1139–43. PMID 7340337.
• Kaushal GP, Walker PD, Shah SV (1994). "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. doi:10.1083/jcb.126.5.1319. PMC 2120165. PMID 8063866.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Dumermuth E, Eldering JA, Grünberg J, et al. (1994). "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. doi:10.1016/0014-5793(93)80421-P. PMID 8262185.
• Bankus JM, Bond JS (1996). "Expression and distribution of meprin protease subunits in mouse intestine". Arch. Biochem. Biophys. 331 (1): 87–94. doi:10.1006/abbi.1996.0286. PMID 8660687.
• Chevallier S, Ahn J, Boileau G, Crine P (1996). "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. doi:10.1042/bj3170731. PMC 1217546. PMID 8760356.
• Eldering JA, Grünberg J, Hahn D, et al. (1997). "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. doi:10.1111/j.1432-1033.1997.00920.x. PMID 9288916.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Lottaz D, Hahn D, Müller S, et al. (1999). "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. doi:10.1046/j.1432-1327.1999.00071.x. PMID 9914532.
• Richter R, Schulz-Knappe P, Schrader M, et al. (1999). "Composition of the peptide fraction in human blood plasma: database of circulating human peptides". J. Chromatogr. B. 726 (1–2): 25–35. doi:10.1016/S0378-4347(99)00012-2. PMID 10348167.
• Köhler D, Kruse M, Stöcker W, Sterchi EE (2000). "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. doi:10.1016/S0014-5793(99)01712-3. PMID 10620696.
• Jiang W, Le B (2000). "Structure and expression of the human MEP1A gene encoding the alpha subunit of metalloendopeptidase meprin A". Arch. Biochem. Biophys. 379 (2): 183–7. doi:10.1006/abbi.2000.1873. PMID 10898933.
• Kumar JM, Bond JS (2001). "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. doi:10.1016/S0167-4781(01)00188-9. PMID 11267665.
• Bertenshaw GP, Turk BE, Hubbard SJ, et al. (2001). "Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity". J. Biol. Chem. 276 (16): 13248–55. doi:10.1074/jbc.M011414200. PMID 11278902.
• Ishmael FT, Norcum MT, Benkovic SJ, Bond JS (2001). "Multimeric structure of the secreted meprin A metalloproteinase and characterization of the functional protomer". J. Biol. Chem. 276 (25): 23207–11. doi:10.1074/jbc.M102654200. PMID 11301339.
• Rösmann S, Hahn D, Lottaz D, et al. (2002). "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. doi:10.1074/jbc.M206203200. PMID 12189145.
• Norman LP, Jiang W, Han X, et al. (2003). "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. doi:10.1128/MCB.23.4.1221-1230.2003. PMC 141138. PMID 12556482.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.