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in other projects wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia human protein muc1 identifiers aliases muc1 admckd admckd1 ca 15 3 cd227 ema h23ag kl 6 mam6 mcd mckd mckd1 muc 1 muc 1 sec muc 1 x muc1 zd pem pemt pum mucin 1 cell surface associated adtkd2 ca15 3 mucin 1 external ids omim 158340 genecards muc1 available structures pdb human uniprot search pdbe rcsb list of pdb id codes 1sm3 2acm gene location human chr chromosome 1 human 1 band 1q22 start 155 185 824 bp 1 end 155 192 916 bp 1 rna expression pattern bgee human mouse ortholog top expressed in pylorus pancreatic ductal cell nasal epithelium right uterine tube cardia olfactory zone of nasal mucosa lower lobe of lung buccal mucosa cell gastric mucosa palpebral conjunctiva n a more reference expression data biogps more reference expression data gene ontology molecular function protein binding transcription coregulator activity rna polymerase ii cis regulatory region sequence specific dna binding p53 binding cellular component extracellular region cytoplasm integral component of membrane nucleus golgi lumen integral component of plasma membrane apical plasma membrane membrane vesicle extracellular exosome extracellular space plasma membrane biological process positive regulation of histone h4 acetylation regulation of transcription from rna polymerase ii promoter in response to stress dna damage response signal transduction by p53 class mediator resulting in cell cycle arrest negative regulation of intrinsic apoptotic signaling pathway in response to dna damage by p53 class mediator negative regulation of cell adhesion mediated by integrin dna damage response signal transduction by p53 class mediator resulting in transcription of p21 class mediator positive regulation of transcription from rna polymerase ii promoter in response to stress o glycan processing negative regulation of transcription by competitive promoter binding stimulatory c type lectin receptor signaling pathway cytokine mediated signaling pathway sources amigo quickgo orthologs databases ncbi entry oma entry species human mouse entrez 4582 n a ensembl ensg00000185499 n a uniprot p15941 q7z551 n a refseq mrna nm_001018016 nm_001018017 nm_001018021 nm_001044390 nm_001044391 nm_001044392 nm_001044393 nm_001204285 nm_001204286 nm_001204287 nm_001204288 nm_001204289 nm_001204290 nm_001204291 nm_001204292 nm_001204293 nm_001204294 nm_001204295 nm_001204296 nm_001204297 nm_002456 nm_182741 nm_001371720 n a refseq protein np_001018016 np_001018017 np_001037855 np_001037856 np_001037857 np_001037858 np_001191214 np_001191215 np_001191216 np_001191217 np_001191218 np_001191219 np_001191220 np_001191221 np_001191222 np_001191223 np_001191224 np_001191225 np_001191226 np_002447 np_001358649 np_001191217 1 np_001191225 1 np_001037856 1 n a location ucsc chr 1 155 19 155 19 mb n a pubmed search 2 n a wikidata view edit human mucin short variant s1 also called polymorphic epithelial mucin pem or epithelial membrane antigen ema is a mucin encoded by the muc1 gene in humans 3 mucin short variant s1 is a glycoprotein with extensive o linked glycosylation of its extracellular domain mucins line the apical surface of epithelial cells in the lungs stomach intestines eyes and several other organs 4 mucins protect the body from infection by pathogen binding to oligosaccharides in the extracellular domain preventing the pathogen from reaching the cell surface 5 overexpression of muc1 is often associated with colon breast ovarian lung and pancreatic cancers 6 joyce taylor papadimitriou identified and characterised the antigen during her work with breast and ovarian tumors structure edit muc1 is a member of the mucin family and encodes a membrane bound glycosylated phosphoprotein muc1 has a core protein mass of 120 225 kda which increases to 250 500 kda with glycosylation it extends 200 500 nm beyond the surface of the cell 7 the protein is anchored to the apical surface of many epithelia by a transmembrane domain beyond the transmembrane domain is a sea domain that contains a cleavage site for release of the large extracellular domain the release of mucins is performed by sheddases 8 the extracellular domain includes a 20 amino acid variable number tandem repeat vntr domain with the number of repeats varying from 20 to 120 in different individuals these repeats are rich in serine threonine and proline residues which permits heavy o glycosylation 7 multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported but the full length nature of only some has been determined 9 muc1 is cleaved in the endoplasmic reticulum into two pieces the cytoplasmic tail including the transmembrane domain and the extracellular domain these domains tightly associate in a non covalent fashion 10 this tight non covalent association is not broken by treatment with urea low ph high salt or boiling treatment with sodium dodecyl sulfate triggers dissociation of the subunits 11 the cytoplasmic tail of muc1 is 72 amino acids long and contains several phosphorylation sites 12 function edit the protein serves a protective function by binding to pathogens 13 and also functions in a cell signaling capacity 12 overexpression aberrant intracellular localization and changes in glycosylation of this protein have been associated with carcinomas e g the canag tumour antigen is a novel glycoform of muc1 14 in the cell nucleus the protein muc1 regulates the activity of transcription factor complexes that have a documented role in tumor induced changes of host immunity 15 interactions edit muc1 has been shown to interact with ctnnd1 16 erbb2 17 18 grb2 19 jup 17 and sos1 18 19 role in cancer edit the ability of chemotherapeutic drugs to access the cancer cells is inhibited by the heavy glycosylation in the extracellular domain of muc1 the glycosylation creates a highly hydrophilic region which prevents hydrophobic chemotherapeutic drugs from passing through this prevents the drugs from reaching their targets which usually reside within the cell similarly the glycosylation has been shown to bind to growth factors this allows cancer cells which produce a large amount of muc1 to concentrate growth factors near their receptors increasing receptor activity and the growth of cancer cells muc1 also prevents the interaction of immune cells with receptors on the cancer cell surface through steric hindrance this inhibits an anti tumor immune response 4 preventing cell death edit muc1 cytoplasmic tail has been shown to bind to p53 this interaction is increased by genotoxic stress muc1 and p53 were found to be associated with the p53 response element of the p21 gene promoter this results in activation of p21 which results in cell cycle arrest association of muc1 with p53 in cancer results in inhibition of p53 mediated apoptosis and promotion of p53 mediated cell cycle arrest 20 overexpression of muc1 in fibroblasts increased the phosphorylation of akt phosphorylation of akt results in phosphorylation of bcl 2 associated death promoter this results in dissociation of bcl 2 associated death promoter with bcl 2 and bcl xl activation was shown to be dependent on the upstream activation of pi3k additionally muc1 was shown to increase expression of bcl xl overexpression of muc1 in cancer the presence of free bcl 2 and bcl xl prevents the release of cytochrome c from mitochondria thereby preventing apoptosis 21 muc1 cytoplasmic tail is shuttled to the mitochondria through interaction with hsp90 this interaction is induced through phosphorylation of the muc1 cytoplasmic tail by src gene src is activated by the egf receptor family ligand neuregulin the cytoplasmic tail is then inserted into the mitochondrial outer membrane localization of muc1 to the mitochondria prevents the activation of apoptotic mechanisms 22 promoting tumor invasion edit muc1 cytoplasmic tail was shown to interact with beta catenin a sxxxxxssl motif was identified in muc1 that is conserved with other beta catenin binding partners this interaction was shown to be dependent on cell adhesion 23 studies have demonstrated that muc1 is phosphorylated on a yekv motif phosphorylation of this site has been demonstrated by lyn through mediation of interleukin 7 24 src through mediation of egfr 25 26 and prkcd 27 this interaction is antagonized by degradation of beta catenin by gsk3b muc1 blocks the phosphorylation dependent degradation of beta catenin by gsk3b 28 29 the result is that increased expression of muc1 in cancer increases stabilized beta catenin this promotes the expression of vimentin and cdh2 these proteins are associated with a mesenchymal phenotype characterized by increased motility and invasiveness in cancer cells increased expression of muc1 promotes cancer cell invasion through beta catenin resulting in the initiation of epithelial mesenchymal transition which promotes the formation of metastases 30 31 diagnostic uses edit blood tests cancer antigens ca 27 29 and 15 3 edit ca 27 29 a k a br 27 29 and ca 15 3 measure different epitopes of the same protein antigen product of the muc1 gene seen in breast cancer ca 27 29 has enhanced sensitivity and specificity compared to ca 15 3 and is elevated in 30 of patients with low stage disease and 60 to 70 of patients with advanced stage breast cancer ca 27 29 levels over 100 u ml and ca 15 3 levels over 25 u ml are rare in benign conditions and suggest malignancy immunohistochemistry edit using immunohistochemistry muc1 can be identified in a wide range of secretory epithelia and their neoplastic equivalents 32 it is a marker of various types of cancer see below 32 in micropapillary carcinoma of the breast and bladder muc1 stains the stroma facing surface of cell clusters of micropapillary units 32 it can distinguish systemic anaplastic large cell lymphoma muc1 positive from cutaneous anaplastic large cell lymphoma usually muc1 negative 32 although other antibodies such as cytokeratins are more commonly used for the identification of metastatic carcinoma deposits ema can be used to distinguish mesothelioma in which it is restricted to the cell membranes and associated micovilli from adenocarcinoma in which it is diffusely spread through the cytoplasm 33 diseases with positive muc1 staining 32 adenocarcinomas breast cancer colorectal cancer pancreatic cancer carcinoid tumor chordoma choriocarcinoma desmoplastic small round cell tumor epithelioid sarcoma follicular dendritic cell sarcoma interdigitating dendritic cell sarcoma reticulum cell sarcoma lung type ii cell lesions hyperplasia dysplasia lymphomas anaplastic large cell lymphoma diffuse large b cell lymphoma variable expression plasmablastic lymphoma primary effusion lymphoma meningioma mesotheliomas epithelioid myeloma paget s disease of the breast perineurioma plasmacytomas renal cell carcinoma synovial sarcoma epithelial areas thymic carcinoma often negative staining 32 myoepithelial cells adrenocortical carcinoma hepatocellular carcinoma germ cell tumors except choriocarcinoma acquired cystic kidney disease associated renal cell carcinoma leiomyosarcoma usually liposarcoma melanoma neuroblastoma paraganglioma solitary fibrous tumor normal tissues with positive staining 32 apical surface of almost all glandular and ductal epithelial cells breast including toker cells distal convoluted tubule of kidney type ii cells of pulmonary alveoli pancreas salivary glands eccrine and apocrine glands of the skin several white blood cells activated t cells some b cells monocytes follicular dendritic cells perineurial cells as a therapeutic drug target edit using muc1 vaccines are being tested against a type of blood cancer called multiple myeloma the technology could in theory be applied to 90 percent of all known cancers including prostate and breast cancer solid and non solid tumors this method would activate the immune system by training t cells to search out and destroy cells that display a specific molecule or marker of muc1 muc1 is found on nearly all epithelial cells but it is over expressed in cancer cells and its associated glycans are shorter than those of non tumor associated muc1 34 because muc1 is overexpressed and differently glycosylated in many cancers it has been investigated as a drug target e g for the muc1 vaccine ont 10 which has had a phase 1 clinical study 35 see also edit cluster of differentiation list of histologic stains that aid in diagnosis of cutaneous conditions mucin 1 references edit 1 2 3 grch38 ensembl release 89 ensg00000185499 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine gendler sj lancaster ca taylor papadimitriou j duhig t peat n burchell j pemberton l lalani en wilson d september 1990 molecular cloning and expression of human tumor associated polymorphic epithelial mucin the journal of biological chemistry 265 25 15286 93 doi 10 1016 s0021 9258 18 77254 2 pmid 1697589 1 2 hollingsworth ma swanson bj january 2004 mucins in cancer protection and control of the cell surface nature reviews cancer 4 1 45 60 doi 10 1038 nrc1251 pmid 14681689 s2cid 23171728 moncada dm kammanadiminiti sj chadee k july 2003 mucin and toll like receptors in host defense against intestinal parasites trends parasitol 19 7 305 311 doi 10 1016 s1471 4922 03 00122 3 pmid 12855381 gendler sj july 2001 muc1 the renaissance molecule j mammary gland biol neoplasia 6 3 339 353 doi 10 1023 a 1011379725811 pmid 11547902 s2cid 32520673 1 2 brayman m thathiah a carson dd january 2004 muc1 a multifunctional cell surface component of reproductive tissue epithelia reprod biol endocrinol 2 4 doi 10 1186 1477 7827 2 4 pmc 320498 pmid 14711375 hattrup cl gendler sj 2008 structure and function of the cell surface tethered mucins annual review of physiology 70 431 57 doi 10 1146 annurev physiol 70 113006 100659 pmid 17850209 entrez gene sea domain of muc1 ligtenberg mj kruijshaar l buijs f van meijer m litvinov sv hilkens j march 1992 cell associated episialin is a complex containing two proteins derived from a common precursor the journal of biological chemistry 267 9 6171 7 doi 10 1016 s0021 9258 18 42677 4 pmid 1556125 julian j carson dd may 2002 formation of muc1 metabolic complex is conserved in tumor derived and normal epithelial cells biochem biophys res commun 293 4 1183 1190 bibcode 2002bbrc 293 1183j doi 10 1016 s0006 291x 02 00352 2 pmid 12054500 1 2 singh pk hollingsworth ma august 2006 cell surface associated mucins in signal transduction trends cell biol 16 9 467 476 doi 10 1016 j tcb 2006 07 006 pmid 16904320 lindén sk sheng yh every al miles km skoog ec florin th sutton p mcguckin ma october 2009 muc1 limits helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy plos pathog 5 10 e1000617 doi 10 1371 journal ppat 1000617 pmc 2752161 pmid 19816567 tolcher aw ochoa l hammond la patnaik a edwards t takimoto c s...