Molecular cloning of seprase: a serine integral membrane protease from human melanoma

• Published in: Biochimica et biophysica acta Vol. 1361; no. 1; pp. 11 - 19
• Main Authors: Goldstein, Leslie A, Ghersi, Giulio, Piñeiro-Sánchez, Mayra L, Monica Salamone, Yeh, Yunyun, Flessate, Denise, Chen, Wen-Tien
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-07-1997
• Subjects: Amino Acid Sequence; Antigens, Neoplasm; Base Sequence; Biomarkers, Tumor; cDNA; Cell Line; Cloning, Molecular; DNA, Complementary - chemistry; DNA, Complementary - genetics; DPPIV; FAP α; Gelatinase; Gelatinases - chemistry; Gelatinases - genetics; Growth Substances - genetics; Humans; Melanoma; Melanoma - enzymology; Membrane Proteins; Molecular Sequence Data; Neoplasm Invasiveness; Seprase; Sequence Alignment; Serine Endopeptidases; Seprase; DPPIV; cDNA; Gelatinase; Melanoma; FAP α
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/S0925-4439(97)00032-X

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 (∼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
α (FAP
α) are products of the same gene. We propose that seprase/FAP
α and DPPIV represent a new subfamily of serine integral membrane proteases (SIMP).