title: Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members.
abstract: A cDNA encoding a new human matrix metalloproteinase (MMP), tentatively called MMP-23, has been cloned from an ovary cDNA library. This protein exhibits sequence similarity with MMPs, but displays a different domain structure. Thus, MMP-23 lacks a recognizable signal sequence and has a short prodomain, although it contains a single cysteine residue that can be part of the cysteine-switch mechanism operating for maintaining enzyme latency. The C-terminal domain is considerably shortened and shows no sequence similarity to hemopexin, whereas all human MMPs, with the exception of matrilysin, contain four hemopexin-like repeats. Furthermore, MMP-23 is devoid of structural features distinctive of the diverse MMP subclasses, including the specific residues located close to the zinc-binding site in collagenases, the transmembrane domain of membrane-type MMPs, or the fibronectin-like domain of gelatinases. Fluorescent in situ hybridization experiments showed that the human MMP-23 gene maps to 1p36, a location which differs from all MMP genes mapped to date. Recombinant MMP-23 produced in Escherichia coli exhibits low, but significant proteolytic activity against a synthetic substrate commonly used for assaying MMPs. Northern blot analysis demonstrated that MMP-23 is predominantly expressed in ovary, testis, and prostate, suggesting that this new MMP may play a specialized role in reproductive processes.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Velasco
authors.forename: A M
authors.initials: AM
authors.lastname: Pendás
authors.forename: A
authors.initials: A
authors.lastname: Fueyo
authors.forename: V
authors.initials: V
authors.lastname: Knäuper
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010053:Ovary / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid