Genomic organization and structure of the 3' region of human MUC3: alternative splicing predicts membrane-bound and soluble forms of the mucin.
The MUC3 gene encodes a large, glycosylated mucin produced by intestinal epithelial cells to form a protective barrier against the external environment. Recently published cDNA sequences for the carboxyl-terminal region of MUC3 polypeptide indicated that rodent Muc3 possesses two epidermal growth factor (EGF)-like domains, and putative transmembrane and cytoplasmic domains, whereas the sequence of human MUC3 predicted termination after the first EGF-like domain. Here we describe the complete genomic sequence encompassing the carboxyl terminal region of human MUC3, revealing the boundaries of 11 exons. RT-PCR and cDNA library cloning experiments indicate that the gene is alternatively spliced, yielding a major membrane-bound form as well as multiple soluble forms. Thus, this work indicates that both membrane-bound and soluble MUC3 mucin proteins are produced by alternative splicing of a single gene. A potentially important polymorphism involving a Tyr residue with a proposed role in signalling is described as well.
Crawley
S C
SC
Department of Medicine, University of California, San Francisco, California 94143, USA.
Gum
J R
JR
Hicks
J W
JW
Pratt
W S
WS
Aubert
J P
JP
Swallow
D M
DM
Kim
Y S
YS
D020413:3' Untranslated Regions / Q000235:genetics*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000737:chemistry; D005091:Exons; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D055263:Mucin-3; D009077:Mucins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D020413:3' Untranslated Regions; C524641:Muc3 protein, mouse; C524651:Muc3 protein, rat; D055263:Mucin-3; D009077:Mucins; D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor