HGNC Approved Gene Symbol: MEP1A
Cytogenetic location: 6p12.3 Genomic coordinates (GRCh38): 6:46,793,389-46,845,984 (from NCBI)
The MEP1A gene encodes the alpha subunit of meprin A (EC 3.4.24.18), a metalloendopeptidase that hydrolyzes a variety of peptide and protein substrates (summary by Bond et al., 1995).
Jiang et al. (1992) reported the cloning and sequencing of the meprin alpha subunit cDNA. The translated polypeptide consists of 760 amino acids, including a preprosequence (77 amino acids) that precedes the N terminus of the purified enzyme. The next 198 amino acids constitute the astacin family protease domain, which includes the astacin family signature sequence. An immunoglobulin/major histocompatibility complex protein signature occurs at the end of the protease domain. At the C terminus there is an epidermal growth factor-like domain followed by a transmembrane domain.
Meprins, members of the 'astacin family' of metalloendopeptidases, are capable of hydrolyzing a variety of peptide and protein substrates. Two forms of meprins, designated A and B (see 600389), were isolated from the kidney of mice, and both hydrolyzed proteins such as azocasein and insulin B chain. Meprin A is the best characterized of the meprins and is known to hydrolyze peptides such as bradykinin, melanocyte-stimulating hormone, neurotensin, luteinizing hormone releasing hormone, transforming growth factor-alpha, and parathyroid hormone. Meprin B from mouse kidney has latent proteolytic activity against polypeptide substrates. Rat meprin A is sometimes referred to as endopeptidase-2 or endopeptidase-24.18; human meprin A is also called N-benzoyl-L-tyrosyl-p-aminobenzoic acid (PABA peptide) hydrolase (PPH). Two types of subunits, alpha and beta, are associated with meprins. The deduced amino acid sequences of these subunits are 45% identical in rodents. Meprin A contains both alpha and beta subunits and is present in the kidney of rats and some strains of mice and in the rat and human intestine. Meprin B, which contains only beta subunits, is present in the kidney of many inbred mouse strains and in intestine of all mice. Therefore, the differential expression of meprin subunits is a mechanism for regulation of tissue-specific gene expression (summary by Bond et al., 1995).
Bond et al. (1995) used radiation hybrids and somatic cell hybrids to map MEP1A to human 6p in a region between the locus for glutathione-S-transferase-A2 (138360), which is located at 6p12-p11, and the centromere. Analyzing somatic cell hybrids, they mapped the MEP1B gene to 18q12.2-q12.3, proximal to the gene encoding transthyretin (TTR; 176300).
Jiang et al. (1995) reported the fine mapping of MEP1A using YAC clones and linkage analysis in autosomal recessive polycystic kidney disease (263200) which maps to 6p21.1-p12. The results from both physical and genetic mapping excluded MEP1A as a candidate for autosomal recessive polycystic kidney disease. Studies placed MEP1A in a region more telomeric to 6p12 and closer to the HLA loci than previously reported. MEP1A was found to be localized between loci at D6S272 and D6S282, close to D6S452, on 6p21.2-p21.1.
By interspecific backcross linkage analysis, Jiang et al. (1992) mapped the gene encoding the alpha subunit, Mep1a, to mouse chromosome 17 near the H-2 complex and Gorbea et al. (1993) mapped the gene for the beta subunit, Mep1b, to mouse chromosome 18. Using fluorescence in situ hybridization, Jiang and Beatty (1997) mapped the Mep1a gene to mouse chromosome 17.
Bond, J. S., Rojas, K., Overhauser, J., Zoghbi, H. Y., 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: 300-303, 1995. [PubMed: 7774936] [Full Text: https://doi.org/10.1016/0888-7543(95)80142-9]
Gorbea, C. M., Marchand, P., Jiang, W., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Bond, J. S. Cloning, expression, and chromosomal localization of the mouse meprin beta subunit. J. Biol. Chem. 268: 21035-21043, 1993. [PubMed: 8407940]
Jiang, W., Beatty, B. G. Assignment of Mep1a to mouse chromosome band 17C1-D1 by in situ hybridization. Cytogenet. Cell Genet. 76: 206-207, 1997. [PubMed: 9186525] [Full Text: https://doi.org/10.1159/000134550]
Jiang, W., Dewald, G., Brundage, E., Mucher, G., Schildhaus, H.-U., Zerres, K., Bond, J. S. Fine mapping of MEP1A, the gene encoding the alpha subunit of the metalloendopeptidase meprin, to human chromosome 6p21. Biochem. Biophys. Res. Commun. 216: 630-635, 1995. [PubMed: 7488157] [Full Text: https://doi.org/10.1006/bbrc.1995.2668]
Jiang, W., Gorbea, C. M., Flannery, A. V., Beynon, R. J., Grant, G. A., Bond, J. S. The alpha subunit of meprin A: molecular cloning and sequencing, differential expression in inbred mouse strains, and evidence for divergent evolution of the alpha and beta subunits. J. Biol. Chem. 267: 9185-9193, 1992. Note: Erratum: J. Biol. Chem. 267: 13779 only, 1992. [PubMed: 1374387]