Complete primary structure of two variant forms of human type XVIII collagen and tissue-specific differences in the expression of the corresponding transcripts.
We report on full-length human type XVIII collagen cDNAs that encode 1516- or 1336-residue alpha 1 (XVIII) chains. The two chains have different signal peptides and variant N-terminal non-collagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains, a 688-residue highly interrupted collagenous portion, and a 312-residue C-terminal non-collagenous portion. Alternative splicing affecting a 43-residue stretch at the junction of the NC1 domain and the beginning of the collagenous portion was identified. The amino acid sequences of the human and previously characterized mouse alpha 1 (XVIII) chains exhibit an overall identity of 79%. The highest homology between these chains was observed in their last 184 residues, corresponding to the proteolytic fragment endostatin, which is capable of inhibiting endothelial cell proliferation, angiogenesis and tumor growth (O'Reilly, et al., Cell 88: 277-285, 1997). Northern analysis of several adult and fetal tissues with a probe for the NC1-493 variant revealed marked amounts of the corresponding 6.2 and 5.0 kb mRNAs in liver, while other tissues contained only faint or undetectable signals. Hybridizations with a probe specific for the NC1-303 variant virtually lacked the liver signal but revealed clear 5.6 and 4.5 kb bands in heart, kidney, placenta, prostate, ovaries, skeletal muscle and small intestine, and faint signals in several other tissues. Thus mRNAs for the long variant occur prominently in liver, while those for the short variant appear to be the major ones in the other tissues analyzed.
Saarela
J
J
Collagen Research Unit, University of Oulu, Finland.
Ylikärppä
R
R
Rehn
M
M
Purmonen
S
S
Pihlajaniemi
T
T
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D043170:Collagen Type XVIII; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000196:embryology; D008099:Liver / Q000737:chemistry / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D043170:Collagen Type XVIII; D018076:DNA, Complementary; D012333:RNA, Messenger; D003094:Collagen