Mucin 4
From Anvita Health Wiki
Contents |
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
Structure
- 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
Compartment
- membrane ( putative), secreted
- isoforms lacking the Cys-rich region, EGF-like domains & transmembrane region are secreted
- secretion occurs by splicing or proteolytic processing
Alternative-splicing
- 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
Expression
- 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
Pathology
- 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,
More General Terms
Internet Database
UniProt: [1]
Entrez gene: 4585
OMIM: 158372
Prosite: [2]
Prosite: [3]
Prosite: [4]
Prosite: [5]
Prosite: [6]
Prosite: [7]
References
