Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease.
The human fibroblast-activation protein (FAP), a member of the serine protease family, was discovered as an inducible type-II cell-surface glycoprotein selectively expressed by reactive stromal fibroblasts of epithelial cancers and healing wounds. Antibodies directed against human FAP have a clinical use for antibody-based tumor imaging. As part of an effort to generate animal models of FAP expression in epithelial tumorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog. In this study, we used PCR/restriction-fragment length polymorphism, identified in interspecific back-crosses between Mus musculus and Mus spretus, to map the Fap gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identified FAP gene locus on human chromosome 2q23. The Fap gene spans approximately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp. This genomic organization is very similar to that of the human FAP locus. Similar to the gene encoding dipeptidyl peptidase IV (DPP IV), the nucleotides encoding the serine protease consensus motif, WGWSYGG, are split between two exons, a feature distinct from classical serine proteases. Consistent with the similarity to DPP IV, a chimeric FAP fusion protein expressed in a baculovirus system has dipeptidyl peptidase activity.
Department of Oncology Research, Boehringer Ingelheim Pharma KG, Biberach an der Riss, Germany.
J
J
Niedermeyer
B
B
Enenkel
J E
JE
Park
M
M
Lenter
W J
WJ
Rettig
K
K
Damm
A
A
Schnapp
D000818:Animals; D000951:Antigens, Neoplasm; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002874:Chromosome Mapping; D017931:DNA Primers; D018076:DNA, Complementary; D010450:Endopeptidases; D005091:Exons; D018093:Gelatinases; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D017931:DNA Primers; D018076:DNA, Complementary; D010450:Endopeptidases; D018093:Gelatinases; D006133:Growth Substances; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha