Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2.
The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal-growth-factor motifs and contains up to ten O-glycosylation and N-glycosylation sites, six of which are differentially glycosylated. Alignment to the translated sequences of Mus. musculus dlk and human dlk revealed 86% and 99% identity, respectively, to a 259-amino-acid residue overlap, and this high similarity extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating FA1 represents the post-translationally modified gene product of human dlk which, in turn, is identical to human adrenal-specific mRNA pG2.
Jensen
C H
CH
Division of Immunology, Statens Seruminstitut, Copenhagen S, Denmark.
Krogh
T N
TN
Højrup
P
P
Clausen
P P
PP
Skjødt
K
K
Larsson
L I
LI
Enghild
J J
JJ
Teisner
B
B
D000595:Amino Acid Sequence; D000653:Amniotic Fluid / Q000737:chemistry*; D000818:Animals; D002276:Carcinoid Tumor / Q000473:pathology; D004815:Epidermal Growth Factor / Q000737:chemistry*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry*; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C064045:delta protein; D004815:Epidermal Growth Factor