Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer.
We have characterized a novel human matrix metalloproteinase (MMP-21) from human placenta DNA complementary to RNA (cDNA). The 569 amino acid translation of the cDNA includes all the typical features of an MMP family member, namely a signal sequence, a prodomain with a PRCGVPD motif, a zinc-binding catalytic domain with an HEIGHVLGL sequence, and a hemopexin-like domain flanked by two cysteine residues. Furthermore, MMP-21 has a furin activation sequence, but no transmembrane sequence nor a cytoplasmic domain. As in Xenopus laevis and Cynops pyrrhogaster there is an additional insertion of approximately 30 amino acids between the prodomain and the catalytic domain, which is poorly conserved between the species and is in human MMP-21 especially proline rich. The MMP-21 gene has seven exons and is located in chromosome 10. This new MMP is the human orthologue for XMMP and CyMMP expressed during gastrulation of X. laevis and C. pyrrhogaster, respectively. A 2.5 kb messenger RNA was observed in fetal liver by Northern analysis. By reverse transcription-polymerase chain reaction, MMP-21 is expressed in various human fetal and adult tissues as well as in cancer cell lines. MMP-21 protein can also be detected in malignancies such as ovarian and colon carcinomas by immunohistochemical staining. Our findings suggest that MMP-21 functions in embryogenesis and tumor progression.
Ahokas
Katja
K
Department of Dermatology, University of Helsinki, and Helsinki University Central Hospital, Meilahdentie 2, FIN-00250, Helsinki, Finland.
Lohi
Jouko
J
Lohi
Hannes
H
Elomaa
Outi
O
Karjalainen-Lindsberg
Marja Liisa
ML
Kere
Juha
J
Saarialho-Kere
Ulpu
U
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007438:Introns; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000235:genetics; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000235:genetics
D018076:DNA, Complementary; D029867:Xenopus Proteins; C471969:MMP21 protein, human; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C106346:XMMP protein, Xenopus