Cloning, expression, and chromosomal localization of the mouse meprin beta subunit.
Meprins are plasma membrane homo- or hetero-oligomeric metalloendopeptidases that contain glycosylated alpha and/or beta subunits. This paper reports the cloning and sequencing of the mouse kidney beta subunit. The primary translation product is composed of 704 amino acids which includes a transient signal sequence of 20 amino acids at the NH2 terminus. The protease domain (Asn-63 to Leu-260) contains the putative zinc-binding motif characteristic of metalloendopeptidases of the "astacin family." The COOH terminus contains an epidermal growth factor-like domain, a potential membrane-spanning domain, and an additional 26 amino acids. The beta subunit has an overall 42% identity to the alpha subunit, however, a 56-amino acid segment near the COOH terminus of alpha is missing in beta, and the putative transmembrane and cytoplasmic domains of the subunits share no significant sequence similarity. NH2-terminal analyses of detergent-solubilized mature forms revealed that, unlike alpha, the prosequence (Leu-21 to Lys-62) is not removed from the beta subunit. Northern blot analysis revealed a 2.5-kilobase message for the beta subunit in the kidney and intestine of C57BL/6 and C3H/He mice. The gene for the beta subunit was localized to mouse chromosome 18. These studies indicate that alpha and beta probably derived from a common ancestral gene, but have evolved so that their genes are on two different chromosomes, and their tissue-specific expression and post-translational processing differ.
Gorbea
C M
CM
Department of Biological Chemistry, Pennsylvania State University College of Medicine, Hershey 17033.
Marchand
P
P
Jiang
W
W
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Bond
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005796:Genes; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D008625:Tiopronin / Q000737:chemistry
D018076:DNA, Complementary; D008625:Tiopronin