Molecular cloning of seprase: a serine integral membrane protease from human melanoma.
Seprase is a homodimeric 170 kDa integral membrane gelatinase whose expression correlates with the invasiveness of the human melanoma cell line LOX. Here, we report the molecular cloning of a cDNA that encodes the 97 kDa subunit of seprase. Its deduced amino acid sequence predicts a type II integral membrane protein with a cytoplasmic tail of 6 amino acids, followed by a transmembrane domain of 20 amino acids and an extracellular domain of 734 amino acids. The carboxyl terminus contains a putative catalytic region (approximately 200 amino acids) which is homologous (68% identity) to that of the nonclassical serine protease dipeptidyl peptidase IV (DPPIV). The conserved serine protease motif G-X-S-X-G is present as G-W-S-Y-G. However, sequence analysis of seprase cDNA from LOX and other cell lines strongly suggests that seprase and human fibroblast activation protein alpha (FAP alpha) are products of the same gene. We propose that seprase/FAP alpha and DPPIV represent a new subfamily of serine integral membrane proteases (SIMP).
Goldstein
L A
LA
Lombardi Cancer Center and Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Ghersi
G
G
Piñeiro-Sánchez
M L
ML
Salamone
M
M
Yeh
Y
Y
Flessate
D
D
Chen
W T
WT
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001483:Base Sequence; D014408:Biomarkers, Tumor; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D010450:Endopeptidases; D018093:Gelatinases / Q000737:chemistry / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000201:enzymology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D016415:Sequence Alignment; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D010450:Endopeptidases; D018093:Gelatinases; D006133:Growth Substances; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha