The amino-terminal sequence of MUC5B contains conserved multifunctional D domains: implications for tissue-specific mucin functions.
The MUC5B mucin gene product is expressed in a wide variety of secretory epithelia including the gallbladder, salivary glands, trachea, and colon. Previous studies by us and others have described the C-terminal region as well as the central tandem repeating domain of this mucin. In an effort to understand the functional role of MUC5B in diverse human tissues, the sequence encoding the N-terminal region of this mucin was determined from the sequences of exons in three overlapping genomic clones. Primer extension mapped the site of transcription initiation 25 bp downstream from a putative TATA box element. The N-terminal region of MUC5B contained 1321 amino acids organized into a signal peptide, a short serine-threonine rich region, and three von Willebrand factor-like D domains. Comparison of this sequence with the N-terminal sequences of MUC2 and MUC5AC revealed a much higher degree of identity (46-59%) than that observed in the C-terminal regions of these mucins (33%). The N-terminal sequence of MUC5B also contains a number of sequence motifs common to several groups of extracellular ligand binding and adhesion proteins not previously recognized in mammalian gel-forming mucins. The N-terminal D domains in MUC5B are likely to have important roles in both mucin assembly and in the protective functions of the secreted mucin.
Offner
G D
GD
Departments of Medicine, Boston University Medical Center, Boston, Massachusetts, USA. goffner@acs.bu.edu
Nunes
D P
DP
Keates
A C
AC
Afdhal
N H
NH
Troxler
R F
RF
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D017931:DNA Primers / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis; D004847:Epithelial Cells; D005704:Gallbladder; D006801:Humans; D008969:Molecular Sequence Data; D055257:Mucin-5B; D009077:Mucins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D016385:TATA Box / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; C524578:MUC5B protein, human; D055257:Mucin-5B; D009077:Mucins; D010446:Peptide Fragments; D020033:Protein Isoforms; D012333:RNA, Messenger; D012313:RNA