Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence.
p97 is a cell-surface glycoprotein that is present in most human melanomas but only in trace amounts in normal adult tissues. To determine the structure of this tumor-associated antigen and to identify its functional domains, we have purified and cloned p97 mRNA and determined its nucleotide sequence. The mRNA encodes a 738-residue precursor, which contains the previously determined N-terminal amino acid sequence of p97. After removal of a 19-residue signal peptide, the mature p97 molecule comprises extracellular domains of 342 and 352 residues and a C-terminal 25-residue stretch of predominantly uncharged and hydrophobic amino acids, which we believe acts as a membrane anchor. Each extracellular domain contains 14 cysteine residues, which form seven intradomain disulfide bridges, and one or two potential N-glycosylation sites. Protease digestion studies show that the three major antigenic determinants of p97 are present on the N-terminal domain. The domains are strikingly homologous to each other (46% amino acid sequence homology) and to the corresponding domains of human serum transferrin (39% homology). Conservation of disulfide bridges and of amino acids thought to compose the iron binding pockets suggests that p97 is also related to transferrin in tertiary structure and function. We propose that p97 be renamed melanotransferrin to denote its original identification in melanoma cells and its evolutionary relationship to serotransferrin and lactotransferrin, the other members of the transferrin superfamily.
T M
TM
Rose
G D
GD
Plowman
D B
DB
Teplow
W J
WJ
Dreyer
K E
KE
Hellström
J P
JP
Brown
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D000939:Epitopes; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D000951:Antigens, Neoplasm; D000939:Epitopes; C000599356:MELTF protein, human; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D004247:DNA