mucin-4; MUC-4; pancreatic adenocarcinoma mucin; testis mucin; ascites sialoglycoprotein; ASGP; tracheobronchial mucin; contains: mucin-4 alpha chain; ascites sialoglycoprotein 1; ASGP-1; contains: mucin-4 beta chain; ascites sialoglycoprotein 2; ASGP-2 (MUC4)

^[1]^[2]^[3]

Function

has anti-adhesive properties
seems to alter cellular behavior through both anti-adhesive effects on cell-cell & cell-extracellular matrix interactions & in its ability to act as an intramembrane ligand for ERBB2
role in cell proliferation & differentiation of epithelial cells by inducing specific phosphorylation of ERBB2
the MUC4-ERBB2 complex causes site-specific phosphorylation of the ERBB2 Tyr-1248
in polarized epithelilal cells, segragates ERBB2 & other ERBB receptors & prevents ERBB2 from acting as a coreceptor
interaction with ERBB2 leads to enhanced expression of CDKN1B
formation of MUC4-ERBB2-ERBB3-NRG1 complex leads to down- regulation of CDKN1B, resulting in repression of apoptosis & stimulation of proliferation
proteolytically cleaved into 2 chains, mucin-4 alpha chain & mucin-4 beta chain
mucin-4 beta chain interacts with ERBB2 via the EGF-like domain 1
in nonpolarized cells, associates with ERBB2 & ERBB3

heterodimeric complex, composed of a mucin-4 alpha chain & a cysteine-rich transmembrane mucin-4 beta chain
mucin-4 alpha chain is highly O-glycosylated
mucin-4 beta chain is predominantly N-glycosylated
contains 1 AMOP domain
contains 2 EGF-like domains
contains 1 NIDO domain
contains 1 VWFD domain

named isoforms=14;
additional isoforms exist
some may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, & mammary & salivary glands
expressed in carcinomas arising from some epithelia, including:
- lung cancers
- squamous cell carcinomas of the upper aerodigestive tract
- mammary carcinomas
- biliary tract neoplasm
- colorectal adenocarcinoma
- cervical cancers
minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors & pancreatic tumor cell lines
expressed early in the primitive gut before respiratory & digestive epithelial cells have acquired their tissue & cell specificity
expressed at the basal surface of the epithelium from 14-26 weeks & then predominantly localized in only parietal cells
immediately before birth, found in the cytoplasm of the mucous columnar epithelial cells
in the embryo expressed in skin, then disappears late in gestation

may play a role in tumor progression
ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation
expression may predict poor prognosis in patients with invasive ductal carcinoma & intrahepatic cholangiocarcinoma,