Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor.
Secretory mucins consist of a protein backbone that is catenated by disulfide bonds, heavily O-glycosylated, and packaged into storage granules prior to release from cells. In this paper, we identify and sequence cDNAs that encode the amino terminus of the MUC2 protein, a major form of mucin found in human intestines and airways. The protein sequence was found to contain a repetitive element of approximately 350 amino acids with considerable sequence similarity to the D domains of prepro-von Willebrand factor. A total of four of these D domains were found to be present in the MUC2 protein, three in the amino-terminal region, and one in the carboxyl-terminal region. Prepro-von Willebrand factor contains four D domains itself, and the overall positioning of the D domains in the two proteins is similar. Prepro-von Willebrand factor contains a 741 residue pro-protein that has been implicated in both the disulfide-linked oligomerization of von Willebrand factor and its packaging into secretory vacuoles. A similar region is present in the MUC2 amino terminus sequence, suggesting that the mechanisms involved in the polymerization and packaging of MUC2 may parallel those already described for von Willebrand factor.
Gum
J R
JR
Gastrointestinal Research Laboratory (151M2), Department of Veterans Affairs Medical Center, San Francisco, California.
Hicks
J W
JW
Toribara
N W
NW
Siddiki
B
B
Kim
Y S
YS
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003106:Colon / Q000378:metabolism; D016384:Consensus Sequence; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014841:von Willebrand Factor / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D009363:Neoplasm Proteins; D011498:Protein Precursors; D011994:Recombinant Proteins; D014841:von Willebrand Factor; C050818:prepro-von Willebrand factor