| This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate spalternative products:Additional isoforms seem to exist,caution:O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats. Experimental sites were determined in a synthetic peptide glycosylated in vitro (PubMed:7744025, PubMed:9597769).,caution:The N-terminal sequence has been shown (PubMed:11341784) to begin at position 24 or 28.,developmental stage:During fetal development, expressed at low levels in the colonic epithelium from 13 weeks of gestation.,function:The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.,function:The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, Src and NF-kappaB pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates P53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of P53 and represses P53 activity.,polymorphism:The number of repeats is highly polymorphic. It varies from 21 to 125 in the northern European population. The most frequent alleles contains 41 and 85 repeats. The tandemly repeated icosapeptide underlies polymorphism at three positions: PAPGSTAP[PAQT]AHGVTSAP[DT/ES]R, DT -> ES and the single replacements P -> A, P -> Q and P-> T. The most frequent replacement DT > ES occurs in up to 50% of the repeats.,PTM:Dual palmitoylation on cysteine residues in the CQC motif is required for recycling from endosomes back to the plasma membrane.,PTM:Highly glycosylated (N- and O-linked carbohydrates and sialic acid). O-glycosylated to a varying degree on serine and threonine residues within each tandem repeat, ranging from mono- to penta-glycosylation. The average density ranges from about 50% in human milk to over 90% in T47D breast cancer cells. Further sialylation occurs during recycling. Membrane-shed glycoproteins from kidney and breast cancer cells have preferentially sialyated core 1 structures, while secreted forms from the same tissues display mainly core 2 structures. The O-glycosylated content is overlapping in both these tissues with terminal fucose and galactose, 2- and 3-linked galactose, 3- and 3,6-linked GalNAc-ol and 4-linked GlcNAc predominating. Differentially O-glycosylated in breast carcinomas with 3,4-linked GlcNAc. N-glycosylation consists of high-mannose, acidic complex-type and hybrid glycans in the secreted form MUC1/SEC, and neutral complex-type in the transmembrane form, MUC1/TM.,PTM:Phosphorylated on tyrosines and serine residues in the C-terminal. Phosphorylation on tyrosines in the C-terminal increases the nuclear location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation of the beta-catenin/E-cadherin complex. Sr |
