MGP Database

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MGP001981

UniProt Annotations

Entry Information
Gene Namemucin 4, cell surface associated
Protein EntryMUC4_HUMAN
UniProt IDQ99102
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=14; Comment=Additional isoforms exist.; Name=1; IsoId=Q99102-1; Sequence=Displayed; Name=2; Synonyms=Sv12, Sv13; IsoId=Q99102-2; Sequence=VSP_022658, VSP_022659; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=3; Synonyms=Sv20; IsoId=Q99102-3; Sequence=VSP_022674, VSP_022675; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=5; Synonyms=Sv18, Sv19; IsoId=Q99102-5; Sequence=VSP_022661, VSP_022669, VSP_022670; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=7; Synonyms=Sv16; IsoId=Q99102-7; Sequence=VSP_022656, VSP_022665; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=8; Synonyms=Sv15; IsoId=Q99102-8; Sequence=VSP_022657, VSP_022664; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=9; Synonyms=Sv11; IsoId=Q99102-9; Sequence=VSP_022652, VSP_022655; Note=Dubious isoform produced through aberrant splice sites.; Name=10; Synonyms=Sv3, Sv17; IsoId=Q99102-10; Sequence=VSP_022661; Name=11; Synonyms=Sv2; IsoId=Q99102-11; Sequence=VSP_022653, VSP_022663; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=12; Synonyms=SvX; IsoId=Q99102-12; Sequence=VSP_022650; Note=May be preferentially expressed in tumor tissues.; Name=13; Synonyms=SvY; IsoId=Q99102-13; Sequence=VSP_022651; Note=May be preferentially expressed in tumor tissues.; Name=15; Synonyms=Sv1; IsoId=Q99102-15; Sequence=VSP_022654, VSP_022662; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=16; Synonyms=Sv6; IsoId=Q99102-16; Sequence=VSP_022671, VSP_022673; Note=Dubious isoform produced through aberrant splice sites.; Name=17; Synonyms=Sv8; IsoId=Q99102-17; Sequence=VSP_022672; Note=Dubious isoform produced through aberrant splice sites.;
Developmental StageExpressed early in the primitive gut before respiratory and digestive epithelial cells have acquired their tissue and cell specificity. Expressed at the basal surface of the epithelium from week 14 to 26 weeks and 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. {ECO:0000269|PubMed:16914178}.
FunctionMay play a role in tumor progression. Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Has anti-adhesive properties. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ERBB2. Plays an important role in cell proliferation and 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 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. {ECO:0000269|PubMed:12102554, ECO:0000269|PubMed:16049287, ECO:0000269|PubMed:16814944, ECO:0000269|PubMed:16914178}.
MiscellaneousExpression is a very useful predictor of poor prognosis in patients with invasive ductal carcinoma and intrahepatic cholangiocarcinoma, mass forming type (IDC,ICC-MF). Patients with IDC or ICC-MF who have high MUC4 expression had a worse survival rate than those with low MUC4 expression.
Ptmmucin-4 beta chain is predominantly N-glycosylated. {ECO:0000269|PubMed:18780401}.
Ptmmucrnin-4 alpha chain is highly O-glycosylated. {ECO:0000269|PubMed:18780401}.
PtmProteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain.
Sequence CautionSequence=AAA63230.1; Type=Miscellaneous discrepancy; Note=May be derived from an intron translation.; Evidence={ECO:0000305}; Sequence=CAC14139.1; Type=Frameshift; Positions=1171; Evidence={ECO:0000305}; Sequence=CAC14141.1; Type=Frameshift; Positions=1256; Evidence={ECO:0000305};
SimilarityContains 1 AMOP domain. {ECO:0000255|PROSITE- ProRule:PRU00347}.
SimilarityContains 1 NIDO domain. {ECO:0000255|PROSITE- ProRule:PRU00570}.
SimilarityContains 1 VWFD domain. {ECO:0000255|PROSITE- ProRule:PRU00580}.
SimilarityContains 2 EGF-like domains. {ECO:0000255|PROSITE- ProRule:PRU00076}.
Subcellular LocationIsoform 11: Secreted.
Subcellular LocationIsoform 15: Secreted.
Subcellular LocationIsoform 17: Cell membrane; Single-pass membrane protein.
Subcellular LocationIsoform 3: Cell membrane; Single-pass membrane protein.
Subcellular LocationMembrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. Secreted {ECO:0000269|PubMed:12102554}. Note=Isoforms lacking the Cys-rich region, EGF-like domains and transmembrane region are secreted. Secretion occurs by splicing or proteolytic processing.
Subcellular LocationMucin-4 alpha chain: Secreted.
Subcellular LocationMucin-4 beta chain: Cell membrane; Single- pass membrane protein.
SubunitA heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain. Mucin- 4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3 (By similarity). {ECO:0000250}.
Tissue SpecificityExpressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands. Expressed in carcinomas arising from some of these epithelia, such as lung cancers, squamous cell carcinomas of the upper aerodigestive tract, mammary carcinomas, biliary tract, colon, and cervix cancers. Minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors and pancreatic tumor cell lines. {ECO:0000269|PubMed:10024507, ECO:0000269|PubMed:10880978, ECO:0000269|PubMed:10920259, ECO:0000269|PubMed:16814944}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MUC4ID41459ch3q29.html";
Web ResourceName=Mucin database; URL="http://www.medkem.gu.se/mucinbiology/databases/";
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