MUC5AC gene approximately extends 150 kb-long on the chromosome 11 in the region p15.5. The central region has sequences repeated in tandem (TR) with a consensus motif composed of 24 bp. The variable number of TR (VNTR) polymorphism is low compared with MUC2 and MUC6. The MUC5AC alleles present small differences in length, but the tandem repeat sequence is highly polymorphic and differs in length by 0.5-1 kb.

To date, there is a discrepancy regarding the total number of exons present in MUC5AC gene. The full size 5 UTR of MUC5AC has not been yet determined, but it is estimated that the mRNA length is approximately 17.5 kb.
The 4 kb fragment upstream is essential for the cell-specific expression of MUC5AC. It contains a TATA box at -29/-23 and potential transcription factor binding sites are described for NFkappaB, Sp-1, GRE and AP-2. One CACCC box able to bind SP1 and initiate transcription has been identified. At present no splice variant forms have been reported.
The MUC5AC promoter has lower number of CpG dinucleotides compared to the other mucin genes located at 11p15, and no silencing of this gene could be explained by methylation.
Several factors have been shown to induce the transcription of MUC5AC such as cytokines, inflammatory mediators, growth factors, some bacterial exproducts and toxic agents like tobacco smoke and pollutants. Furthermore, it is reported that glucocorticoids downregulate MUC5AC expression.

MUC5AC is a secreted, gel-forming mucin with a high molecular weight (approximately 641 kDa). Up to 80% of the total weight is due to the large number of O-glycosilated chains attached to Thr and Ser residues in the TR sequence.

MUC5AC is a polymeric mucin with a N-terminal region, a central region, and a C-terminal region.
At the N-terminal region, D1, D2, D and D3 cysteine-rich domains (Cys) similar to von Willebrand factor (vWF) are present, and are responsible for the disulfide-mediated polymer formation. At the central region, coded by a single large exon, nine Cys domains are located: Cys1 to Cys5 are interspersed by domains rich in Ser, Thr and Pro (STP) with no repetitive sequences, whereas Cys5 to Cys9 domains are interspersed by four TR domains. The consensus repetitive sequence most frequent is TTSTTSAP containing a high number of potential O-glycosilation sites. The C-terminal region has the cysteine-rich vWF-like domains D4, B, C and CK. The CK domain mediates the formation of disulfide-linked dimmers by an autocatalytic process. Towards the C-terminus, contains an autocatalytic protein-cleavage site at the motif GDPH.

MUC5AC was initially isolated from a human tracheobronchial cDNA library, and it is highly expressed in the goblet cells of the respiratory epithelium. MUC5AC is also highly detected in the superficial gastric epithelium, and it is also expressed in pancreas, endocervix and gallbladder.
Under pathological conditions, MUC5AC expression can be altered, as it is reported below. The changes associated with neoplastic transformation and inflammatory diseases, can be induced by the activation of signaling pathways in response to several factors such as inflammatory cytokines, growth factors, and bacterial products.

MUC5AC is a gel-forming mucin and it is a major constituent of the mucus lining mainly the respiratory tract and the stomach. In the surface of the normal respiratory epithelium, MUC5AC is one of the major contributors to the rheological properties of the mucus that has a critical role in the defense against pathogenic and environmental challenges. In the gastric mucosa, MUC5AC and MUC6 are the main components of the protective layer over the surface, and act as a selective diffusion barrier for HCl. MUC5AC also protect the gastric epithelium from Helicobacter pylori, and the glycan structures on MUC5AC, Le^b and sialyl Le^x, act as ligands for the bacterium competing with the ligands located on the epithelial cell surface.

Several orthologues of MUC5AC have been identified in Mus musculus, Rattus norvegicus, Canis lupus familiaris, Equus caballus and Pan troglodytes. The chicken, horse and mouse Muc5AC have a similar domain structure. Murine N-terminal and C-terminal regions showed striking similarities with human MUC5AC, whereas the TSP domains are specific for species. Furthermore, MUC5AC tissue-specific expression is conserved in murine and equine organisms.