MUC1_HUMAN
ID MUC1_HUMAN Reviewed; 1255 AA.
AC P15941; A5YRV1; A6ZID9; A6ZIE0; B1AVQ8; B1AVR0; B6ECA1; E7ESE5; E7EUG9;
AC P13931; P15942; P17626; Q0VAP5; Q0VAP6; Q14128; Q14876; Q16437; Q16442;
AC Q16615; Q6S4Y3; Q7Z547; Q7Z548; Q7Z550; Q7Z552; Q9BXA4; Q9UE75; Q9UE76;
AC Q9UQL1; Q9Y4J2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Mucin-1;
DE Short=MUC-1;
DE AltName: Full=Breast carcinoma-associated antigen DF3;
DE AltName: Full=Cancer antigen 15-3;
DE Short=CA 15-3;
DE AltName: Full=Carcinoma-associated mucin;
DE AltName: Full=Episialin;
DE AltName: Full=H23AG;
DE AltName: Full=Krebs von den Lungen-6;
DE Short=KL-6;
DE AltName: Full=PEMT;
DE AltName: Full=Peanut-reactive urinary mucin;
DE Short=PUM;
DE AltName: Full=Polymorphic epithelial mucin;
DE Short=PEM;
DE AltName: Full=Tumor-associated epithelial membrane antigen;
DE Short=EMA;
DE AltName: Full=Tumor-associated mucin;
DE AltName: CD_antigen=CD227;
DE Contains:
DE RecName: Full=Mucin-1 subunit alpha;
DE Short=MUC1-NT;
DE Short=MUC1-alpha;
DE Contains:
DE RecName: Full=Mucin-1 subunit beta;
DE Short=MUC1-beta;
DE AltName: Full=MUC1-CT;
DE Flags: Precursor;
GN Name=MUC1; Synonyms=PUM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreatic carcinoma;
RX PubMed=2394722; DOI=10.1016/s0021-9258(18)77255-4;
RA Lan M.S., Batra S.K., Qi W.-N., Metzgar R.S., Hollingsworth M.A.;
RT "Cloning and sequencing of a human pancreatic tumor mucin cDNA.";
RL J. Biol. Chem. 265:15294-15299(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=2318825; DOI=10.1016/s0021-9258(19)39399-8;
RA Ligtenberg M.J.L., Vos H.L., Gennissen A.M.C., Hilkens J.;
RT "Episialin, a carcinoma-associated mucin, is generated by a polymorphic
RT gene encoding splice variants with alternative amino termini.";
RL J. Biol. Chem. 265:5573-5578(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary carcinoma;
RX PubMed=1697589; DOI=10.1016/s0021-9258(18)77254-2;
RA Gendler S.J., Lancaster C.A., Taylor-Papadimitriou J., Duhig T., Peat N.,
RA Burchell J., Pemberton L., Lalani E.-N., Wilson D.;
RT "Molecular cloning and expression of human tumor-associated polymorphic
RT epithelial mucin.";
RL J. Biol. Chem. 265:15286-15293(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=2268309; DOI=10.1016/s0006-291x(05)80888-5;
RA Lancaster C.A., Peat N., Duhig T., Wilson D., Taylor-Papadimitriou J.,
RA Gendler S.J.;
RT "Structure and expression of the human polymorphic epithelial mucin gene:
RT an expressed VNTR unit.";
RL Biochem. Biophys. Res. Commun. 173:1019-1029(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Mammary carcinoma;
RX PubMed=2351132; DOI=10.1111/j.1432-1033.1990.tb15511.x;
RA Wreschner D.H., Hareuveni M., Tsarfaty I., Smorodinsky N., Horev J.,
RA Zaretsky J., Kotkes P., Weiss M., Lathe R., Dion A., Keydar I.;
RT "Human epithelial tumor antigen cDNA sequences. Differential splicing may
RT generate multiple protein forms.";
RL Eur. J. Biochem. 189:463-473(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary carcinoma;
RX PubMed=2112460; DOI=10.1111/j.1432-1033.1990.tb15512.x;
RA Hareuveni M., Tsarfaty I., Zaretsky J., Kotkes P., Horev J., Zrihan S.,
RA Weiss M., Green S., Lathe R., Keydar I., Wreschner D.H.;
RT "A transcribed gene, containing a variable number of tandem repeats, codes
RT for a human epithelial tumor antigen. cDNA cloning, expression of the
RT transfected gene and over-expression in breast cancer tissue.";
RL Eur. J. Biochem. 189:475-486(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1688329; DOI=10.1016/0378-1119(90)90242-j;
RA Tsarfaty I., Hareuveni M., Horev J., Zaretsky J., Weiss M., Jeltsch J.-M.,
RA Garnier J.-M., Lathe R., Keydar I., Wreschner D.H.;
RT "Isolation and characterization of an expressed hypervariable gene coding
RT for a breast-cancer-associated antigen.";
RL Gene 93:313-318(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM Y).
RX PubMed=7925397; DOI=10.1111/j.1432-1033.1994.00787.x;
RA Zrihan-Licht S., Vos H.L., Baruch A., Elroy-Stein O., Sagiv D., Keydar I.,
RA Hilkens J., Wreschner D.H.;
RT "Characterization and molecular cloning of a novel MUC1 protein, devoid of
RT tandem repeats, expressed in human breast cancer tissue.";
RL Eur. J. Biochem. 224:787-795(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; Y AND 8), AND TISSUE SPECIFICITY.
RX PubMed=9212228;
RX DOI=10.1002/(sici)1097-0215(19970703)72:1<87::aid-ijc13>3.0.co;2-7;
RA Oosterkamp H.M., Scheiner L., Stefanova M.C., Lloyd K.O., Finstad C.L.;
RT "Comparison of MUC-1 mucin expression in epithelial and non-epithelial
RT cancer cell lines and demonstration of a new short variant form (MUC-
RT 1/Z).";
RL Int. J. Cancer 72:87-94(1997).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZD).
RX PubMed=15623537; DOI=10.1074/jbc.m406943200;
RA Levitin F., Baruch A., Weiss M., Stiegman K., Hartmann M.L.,
RA Yoeli-Lerner M., Ziv R., Zrihan-Licht S., Shina S., Gat A., Lifschitz B.,
RA Simha M., Stadler Y., Cholostoy A., Gil B., Greaves D., Keydar I.,
RA Zaretsky J., Smorodinsky N., Wreschner D.H.;
RT "A novel protein derived from the MUC1 gene by alternative splicing and
RT frameshifting.";
RL J. Biol. Chem. 280:10655-10663(2005).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6; E2; J13; M6; S2; T10; Y-LSP AND
RP ZD), ALTERNATIVE SPLICING, AND VARIANT MET-1117.
RX PubMed=22941036; DOI=10.1007/s00262-012-1325-2;
RA Zhang L., Vlad A., Milcarek C., Finn O.J.;
RT "Human mucin MUC1 RNA undergoes different types of alternative splicing
RT resulting in multiple isoforms.";
RL Cancer Immunol. Immunother. 62:423-435(2013).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9).
RC TISSUE=Carcinoma;
RA Zhang L.X., Li C.H., Sun L.Y., Yue W.;
RT "Cloning of a new potential secreted short variant form of MUC1 mucin in
RT epithelial cancer cell line.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM Y), AND VARIANT MET-1117.
RC TISSUE=Cervix carcinoma;
RX PubMed=15969018;
RA Zhang L.X., Li C.H., Sun L.Y., Wang M., Lu H.J.;
RT "Soluble expression of peptide containing MUC1/Y-specific epitope in
RT Escherichia coli and preparation of the antibody.";
RL Sheng Wu Gong Cheng Xue Bao 19:337-342(2003).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM F).
RA Zhang L.X., Lu H.J.;
RT "Cloning of a new MUC1 short variant mRNA F from HeLa cells.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM S2).
RA Zhang L.X., Lu H.J.;
RT "Cloning of a new MUC1 short variant mRNA S2 from HeLa cells.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M6).
RA Zhang L., Finn O.J.;
RT "Isolation of MUC1 isoforms from MCF7 cells.";
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [17]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-1117 AND ASN-1142.
RG NIEHS SNPs program;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [18]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [19]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [20]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS Y AND Y-LSP).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [21]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3417635; DOI=10.1016/s0021-9258(18)37632-4;
RA Gendler S.J., Taylor-Papadimitriou J., Duhig T., Rothbard J., Burchell J.;
RT "A highly immunogenic region of a human polymorphic epithelial mucin
RT expressed by carcinomas is made up of tandem repeats.";
RL J. Biol. Chem. 263:12820-12823(1988).
RN [22]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-160 (ISOFORM 2).
RX PubMed=2597151; DOI=10.1016/s0006-291x(89)80014-2;
RA Abe M., Siddiqui J., Kufe D.;
RT "Sequence analysis of the 5' region of the human DF3 breast carcinoma-
RT associated antigen gene.";
RL Biochem. Biophys. Res. Commun. 165:644-649(1989).
RN [23]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-109 (ISOFORM 2).
RC TISSUE=Thyroid;
RX PubMed=8608966;
RX DOI=10.1002/(sici)1097-0215(19960328)66:1<55::aid-ijc10>3.0.co;2-a;
RA Weiss M., Baruch A., Keydar I., Wreschner D.H.;
RT "Preoperative diagnosis of thyroid papillary carcinoma by reverse
RT transcriptase polymerase chain reaction of the MUC1 gene.";
RL Int. J. Cancer 66:55-59(1996).
RN [24]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-89.
RC TISSUE=Lung;
RX PubMed=8604237; DOI=10.1159/000227547;
RA Yu C.J., Yang P.C., Shew J.Y., Hong T.M., Yang S.C., Lee Y.C., Lee L.N.,
RA Luh K.T., Wu C.W.;
RT "Mucin mRNA expression in lung adenocarcinoma cell lines and tissues.";
RL Oncology 53:118-126(1996).
RN [25]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-46 (ISOFORMS 3 AND 4).
RC TISSUE=Mammary carcinoma;
RA Buluwela L., Liu Q., Luqmani Y.A., Gomm J.J., Coombes R.C.;
RL Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases.
RN [26]
RP PROTEIN SEQUENCE OF 24-33; 28-37 AND 1098-1107, AND PROTEOLYTIC PROCESSING.
RX PubMed=11341784; DOI=10.1006/bbrc.2001.4775;
RA Parry S., Silverman H.S., McDermott K., Willis A., Hollingsworth M.A.,
RA Harris A.;
RT "Identification of MUC1 proteolytic cleavage sites in vivo.";
RL Biochem. Biophys. Res. Commun. 283:715-720(2001).
RN [27]
RP PROTEIN SEQUENCE OF 1098-1111, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP SER-1098.
RX PubMed=15987679; DOI=10.1074/jbc.m506047200;
RA Levitin F., Stern O., Weiss M., Gil-Henn C., Ziv R., Prokocimer Z.,
RA Smorodinsky N.I., Rubinstein D.B., Wreschner D.H.;
RT "The MUC1 SEA module is a self-cleaving domain.";
RL J. Biol. Chem. 280:33374-33386(2005).
RN [28]
RP PROTEIN SEQUENCE OF TANDEM REPEAT, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP GLYCOSYLATION.
RX PubMed=10373415; DOI=10.1074/jbc.274.26.18165;
RA Mueller S., Alving K., Peter-Katalinic J., Zachara N., Gooley A.A.,
RA Hanisch F.-G.;
RT "High density O-glycosylation on tandem repeat peptide from secretory MUC1
RT of T47D breast cancer cells.";
RL J. Biol. Chem. 274:18165-18172(1999).
RN [29]
RP PHOSPHORYLATION.
RX PubMed=7988707; DOI=10.1016/0014-5793(94)01251-2;
RA Zrihan-Licht S., Baruch A., Elroy-Stein O., Keydar I., Wreschner D.H.;
RT "Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins.
RT Cytokine receptor-like molecules.";
RL FEBS Lett. 356:130-136(1994).
RN [30]
RP IDENTIFICATION IN A COMPLEX WITH SOS1 AND GRB2, INTERACTION WITH GRB2 AND
RP SOS1, AND PHOSPHORYLATION.
RX PubMed=7664271;
RA Pandey P., Kharbanda S., Kufe D.;
RT "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the
RT Sos/Ras exchange protein.";
RL Cancer Res. 55:4000-4003(1995).
RN [31]
RP GLYCOSYLATION AT THR-131 AND THR-139, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=7744025; DOI=10.1111/j.1432-1033.1995.0140l.x;
RA Stadie T.R., Chai W., Lawson A.M., Byfield P.G., Hanisch F.G.;
RT "Studies on the order and site specificity of GalNAc transfer to MUC1
RT tandem repeats by UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase
RT from milk or mammary carcinoma cells.";
RL Eur. J. Biochem. 229:140-147(1995).
RN [32]
RP INTERACTION WITH CTNNB1 AND JUP, AND FUNCTION.
RX PubMed=9139698; DOI=10.1074/jbc.272.19.12492;
RA Yamamoto M., Bharti A., Li Y., Kufe D.;
RT "Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-
RT catenin in cell adhesion.";
RL J. Biol. Chem. 272:12492-12494(1997).
RN [33]
RP GLYCOSYLATION.
RX PubMed=9312074; DOI=10.1074/jbc.272.40.24780;
RA Mueller S., Goletz S., Packer N.H., Gooley A.A., Lawson A.M.,
RA Hanisch F.-G.;
RT "Localization of O-glycosylation sites on glycopeptide fragments from
RT lactation-associated MUC1. All putative sites within the tandem repeat are
RT glycosylation targets in vivo.";
RL J. Biol. Chem. 272:24780-24793(1997).
RN [34]
RP DEVELOPMENTAL STAGE.
RX PubMed=9536947; DOI=10.1136/gut.42.2.220;
RA Reid C.J., Harris A.;
RT "Developmental expression of mucin genes in the human gastrointestinal
RT system.";
RL Gut 42:220-226(1998).
RN [35]
RP GLYCOSYLATION AT THR-131 AND THR-139, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=9597769;
RX DOI=10.1002/(sici)1096-9888(199804)33:4<358::aid-jms642>3.0.co;2-3;
RA Hanisch F.G., Green B.N., Bateman R., Peter-Katalinic J.;
RT "Localization of O-glycosylation sites of MUC1 tandem repeats by QTOF ESI
RT mass spectrometry.";
RL J. Mass Spectrom. 33:358-362(1998).
RN [36]
RP INTERACTION WITH GSK3B AND CTNNB1, PHOSPHORYLATION AT SER-1227, AND
RP MUTAGENESIS OF SER-1223 AND SER-1227.
RX PubMed=9819408; DOI=10.1128/mcb.18.12.7216;
RA Li Y., Bharti A., Chen D., Gong J., Kufe D.;
RT "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-
RT associated antigen and beta-catenin.";
RL Mol. Cell. Biol. 18:7216-7224(1998).
RN [37]
RP CHARACTERIZATION (ISOFORM Y), AND MUTAGENESIS OF ASP-1116.
RX PubMed=10197628;
RA Baruch A., Hartmann M.-L., Yoeli M., Adereth Y., Greenstein S., Stadler Y.,
RA Skornik Y., Zaretsky J., Smorodinsky N.I., Keydar I., Wreschner D.H.;
RT "The breast cancer-associated MUC1 gene generates both a receptor and its
RT cognate binding protein.";
RL Cancer Res. 59:1552-1561(1999).
RN [38]
RP INTERACTION WITH ICAM1.
RX PubMed=11173916; DOI=10.1159/000051917;
RA Hayashi T., Takahashi T., Motoya S., Ishida T., Itoh F., Adachi M.,
RA Hinoda Y., Imai K.;
RT "MUC1 mucin core protein binds to the domain 1 of ICAM-1.";
RL Digestion 63 Suppl. 1:87-92(2001).
RN [39]
RP SUBCELLULAR LOCATION.
RX PubMed=11118479; DOI=10.1177/002215540104900107;
RA Bennett R. Jr., Jaervelae T., Engelhardt P., Kostamovaara L., Sparks P.,
RA Carpen O., Turunen O., Vaheri A.;
RT "Mucin MUC1 is seen in cell surface protrusions together with ezrin in
RT immunoelectron tomography and is concentrated at tips of filopodial
RT protrusions in MCF-7 breast carcinoma cells.";
RL J. Histochem. Cytochem. 49:67-77(2001).
RN [40]
RP INTERACTION WITH SRC; GSK3B AND CTNNB1, PHOSPHORYLATION AT TYR-1229, AND
RP MUTAGENESIS OF TYR-1229.
RX PubMed=11152665; DOI=10.1074/jbc.c000754200;
RA Li Y., Kuwahara H., Ren J., Wen G., Kufe D.;
RT "The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1
RT carcinoma-associated antigen with GSK3 beta and beta-catenin.";
RL J. Biol. Chem. 276:6061-6064(2001).
RN [41]
RP POLYMORPHISM WITHIN THE REPEAT.
RX PubMed=11350974; DOI=10.1074/jbc.m103187200;
RA Engelmann K., Baldus S.E., Hanisch F.-G.;
RT "Identification and topology of variant sequences within individual repeat
RT domains of the human epithelial tumor mucin MUC1.";
RL J. Biol. Chem. 276:27764-27769(2001).
RN [42]
RP INTERACTION WITH EGFR, PHOSPHORYLATION AT TYR-1229 BY EGFR, AND MUTAGENESIS
RP OF TYR-1191; TYR-1203; TYR-1209; TYR-1218 AND TYR-1229.
RX PubMed=11483589; DOI=10.1074/jbc.c100359200;
RA Li Y., Ren J., Yu W., Li Q., Kuwahara H., Yin L., Carraway K.L. III,
RA Kufe D.;
RT "The epidermal growth factor receptor regulates interaction of the human
RT DF3/MUC1 carcinoma antigen with c-Src and beta-catenin.";
RL J. Biol. Chem. 276:35239-35242(2001).
RN [43]
RP PHOSPHORYLATION AT THR-1224, INTERACTION WITH PRKCD, FUNCTION, AND
RP MUTAGENESIS OF SER-1223; THR-1224 AND SER-1227.
RX PubMed=11877440; DOI=10.1074/jbc.m200436200;
RA Ren J., Li Y., Kufe D.;
RT "Protein kinase C delta regulates function of the DF3/MUC1 carcinoma
RT antigen in beta-catenin signaling.";
RL J. Biol. Chem. 277:17616-17622(2002).
RN [44]
RP PHOSPHORYLATION AT TYR-1203; TYR-1212; TYR-1229 AND TYR-1243.
RX PubMed=14521915; DOI=10.1016/j.bbrc.2003.09.030;
RA Wang H., Lillehoj E.P., Kim K.C.;
RT "Identification of four sites of stimulated tyrosine phosphorylation in the
RT MUC1 cytoplasmic tail.";
RL Biochem. Biophys. Res. Commun. 310:341-346(2003).
RN [45]
RP INTERACTION WITH LYN, AND PHOSPHORYLATION.
RX PubMed=12750561; DOI=10.4161/cbt.2.2.282;
RA Li Y., Chen W., Ren J., Yu W.H., Li Q., Yoshida K., Kufe D.;
RT "DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-
RT 7.";
RL Cancer Biol. Ther. 2:187-193(2003).
RN [46]
RP INTERACTION WITH CTNNB1, FUNCTION, AND MUTAGENESIS OF TYR-1229.
RX PubMed=14688481;
RA Huang L., Ren J., Chen D., Li Y., Kharbanda S., Kufe D.;
RT "MUC1 cytoplasmic domain coactivates Wnt target gene transcription and
RT confers transformation.";
RL Cancer Biol. Ther. 2:702-706(2003).
RN [47]
RP INTERACTION WITH ADAM17, AND CLEAVAGE.
RX PubMed=12441351; DOI=10.1074/jbc.m208326200;
RA Thathiah A., Blobel C.P., Carson D.D.;
RT "Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1
RT shedding.";
RL J. Biol. Chem. 278:3386-3394(2003).
RN [48]
RP INTERACTION WITH CTNNB1, AND SUBCELLULAR LOCATION.
RX PubMed=12832415; DOI=10.1074/jbc.m304333200;
RA Wen Y., Caffrey T.C., Wheelock M.J., Johnson K.R., Hollingsworth M.A.;
RT "Nuclear association of the cytoplasmic tail of MUC1 and beta-catenin.";
RL J. Biol. Chem. 278:38029-38039(2003).
RN [49]
RP INTERACTION WITH ERBB2; ERBB3 AND ERBB4, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 1187-ARG--LYS-1189.
RX PubMed=12939402;
RA Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D.;
RT "Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent
RT on the DF3/MUC1 oncoprotein.";
RL Mol. Cancer Res. 1:765-775(2003).
RN [50]
RP INTERACTION WITH AP1S2 AND GRB2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP TYR-1191; TYR-1203; TYR-1229 AND TYR-1243.
RX PubMed=15471854; DOI=10.1074/jbc.m409360200;
RA Kinlough C.L., Poland P.A., Bruns J.B., Harkleroad K.L., Hughey R.P.;
RT "MUC1 membrane trafficking is modulated by multiple interactions.";
RL J. Biol. Chem. 279:53071-53077(2004).
RN [51]
RP INTERACTION WITH TP53, AND FUNCTION.
RX PubMed=15710329; DOI=10.1016/j.ccr.2005.01.008;
RA Wei X., Xu H., Kufe D.;
RT "Human MUC1 oncoprotein regulates p53-responsive gene transcription in the
RT genotoxic stress response.";
RL Cancer Cell 7:167-178(2005).
RN [52]
RP INTERACTION WITH GSK3B, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=16288032; DOI=10.1158/0008-5472.can-05-2474;
RA Huang L., Chen D., Liu D., Yin L., Kharbanda S., Kufe D.;
RT "MUC1 oncoprotein blocks glycogen synthase kinase 3beta-mediated
RT phosphorylation and degradation of beta-catenin.";
RL Cancer Res. 65:10413-10422(2005).
RN [53]
RP ERRATUM OF PUBMED:16288032.
RA Kinlough C.L., Poland P.A., Bruns J.B., Harkleroad K.L., Hughey R.P.;
RL J. Biol. Chem. 280:28827-28827(2005).
RN [54]
RP STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15972891; DOI=10.1093/glycob/cwi099;
RA Engelmann K., Kinlough C.L., Muller S., Razawi H., Baldus S.E.,
RA Hughey R.P., Hanisch F.-G.;
RT "Transmembrane and secreted MUC1 probes show trafficking-dependent changes
RT in O-glycan core profiles.";
RL Glycobiology 15:1111-1124(2005).
RN [55]
RP INTERACTION WITH LCK, PHOSPHORYLATION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15513966; DOI=10.1189/jlb.0604333;
RA Mukherjee P., Tinder T.L., Basu G.D., Gendler S.J.;
RT "MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells
RT and normal T cells.";
RL J. Leukoc. Biol. 77:90-99(2005).
RN [56]
RP PALMITOYLATION AT CYS-1184 AND CYS-1186, SUBCELLULAR LOCATION, INTERACTION
RP WITH AP1S1 AND AP1S2, AND MUTAGENESIS OF CYS-1184; CYS-1186; TYR-1203 AND
RP 1187-ARG--LYS-1189.
RX PubMed=16507569; DOI=10.1074/jbc.m512996200;
RA Kinlough C.L., McMahan R.J., Poland P.A., Bruns J.B., Harkleroad K.L.,
RA Stremple R.J., Kashlan O.B., Weixel K.M., Weisz O.A., Hughey R.P.;
RT "Recycling of MUC1 is dependent on its palmitoylation.";
RL J. Biol. Chem. 281:12112-12122(2006).
RN [57]
RP INTERACTION WITH ESR1.
RX PubMed=16427018; DOI=10.1016/j.molcel.2005.11.030;
RA Wei X., Xu H., Kufe D.;
RT "MUC1 oncoprotein stabilizes and activates estrogen receptor alpha.";
RL Mol. Cell 21:295-305(2006).
RN [58]
RP INTERACTION WITH CTNNB1, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17524503; DOI=10.1016/j.bbamcr.2007.04.009;
RA Lillehoj E.P., Lu W., Kiser T., Goldblum S.E., Kim K.C.;
RT "MUC1 inhibits cell proliferation by a beta-catenin-dependent mechanism.";
RL Biochim. Biophys. Acta 1773:1028-1038(2007).
RN [59]
RP INTERACTION WITH KLF4, AND FUNCTION.
RX PubMed=17308127; DOI=10.1158/0008-5472.can-06-3063;
RA Wei X., Xu H., Kufe D.;
RT "Human mucin 1 oncoprotein represses transcription of the p53 tumor
RT suppressor gene.";
RL Cancer Res. 67:1853-1858(2007).
RN [60]
RP PHOSPHORYLATION AT TYR-1203; TYR-1218 AND TYR-1229, MUTAGENESIS OF TYR-1203
RP AND TYR-1218, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17545600; DOI=10.1158/0008-5472.can-06-4647;
RA Singh P.K., Wen Y., Swanson B.J., Shanmugam K., Kazlauskas A., Cerny R.L.,
RA Gendler S.J., Hollingsworth M.A.;
RT "Platelet-derived growth factor receptor beta-mediated phosphorylation of
RT MUC1 enhances invasiveness in pancreatic adenocarcinoma cells.";
RL Cancer Res. 67:5201-5210(2007).
RN [61]
RP INTERACTION WITH EGFR, AND FUNCTION.
RX PubMed=16983337; DOI=10.1038/sj.onc.1209976;
RA Pochampalli M.R., el Bejjani R.M., Schroeder J.A.;
RT "MUC1 is a novel regulator of ErbB1 receptor trafficking.";
RL Oncogene 26:1693-1701(2007).
RN [62]
RP MARKER IN BREAST CANCER.
RX PubMed=20816948; DOI=10.1016/j.cca.2010.08.039;
RA Duffy M.J., Evoy D., McDermott E.W.;
RT "CA 15-3: uses and limitation as a biomarker for breast cancer.";
RL Clin. Chim. Acta 411:1869-1874(2010).
RN [63]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1227, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [64]
RP INVOLVEMENT IN ADTKD2.
RX PubMed=23396133; DOI=10.1038/ng.2543;
RA Kirby A., Gnirke A., Jaffe D.B., Baresova V., Pochet N., Blumenstiel B.,
RA Ye C., Aird D., Stevens C., Robinson J.T., Cabili M.N., Gat-Viks I.,
RA Kelliher E., Daza R., DeFelice M., Hulkova H., Sovova J., Vylet'al P.,
RA Antignac C., Guttman M., Handsaker R.E., Perrin D., Steelman S.,
RA Sigurdsson S., Scheinman S.J., Sougnez C., Cibulskis K., Parkin M.,
RA Green T., Rossin E., Zody M.C., Xavier R.J., Pollak M.R., Alper S.L.,
RA Lindblad-Toh K., Gabriel S., Hart P.S., Regev A., Nusbaum C., Kmoch S.,
RA Bleyer A.J., Lander E.S., Daly M.J.;
RT "Mutations causing medullary cystic kidney disease type 1 lie in a large
RT VNTR in MUC1 missed by massively parallel sequencing.";
RL Nat. Genet. 45:299-303(2013).
RN [65]
RP STRUCTURE BY NMR OF 1041-1097 AND 1098-1152 OF WILD TYPE AND MUTANT
RP ALA-1098, IDENTIFICATION BY MASS SPECTROMETRY, STRUCTURE OF CARBOHYDRATES,
RP AND AUTOCATALYTIC CLEAVAGE.
RX PubMed=16585136; DOI=10.1093/glycob/cwj110;
RA Parry S., Hanisch F.G., Leir S.H., Sutton-Smith M., Morris H.R., Dell A.,
RA Harris A.;
RT "N-glycosylation of the MUC1 mucin in epithelial cells and secretions.";
RL Glycobiology 16:623-634(2006).
CC -!- FUNCTION: The alpha subunit has cell adhesive properties. Can act both
CC as an adhesion and an anti-adhesion protein. May provide a protective
CC layer on epithelial cells against bacterial and enzyme attack.
CC -!- FUNCTION: The beta subunit contains a C-terminal domain which is
CC involved in cell signaling, through phosphorylations and protein-
CC protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B
CC pathways. In activated T-cells, influences directly or indirectly the
CC Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated
CC transcription and determines cell fate in the genotoxic stress
CC response. Binds, together with KLF4, the PE21 promoter element of TP53
CC and represses TP53 activity.
CC -!- SUBUNIT: The alpha subunit forms a tight, non-covalent heterodimeric
CC complex with the proteolytically-released beta-subunit. Interaction,
CC via the tandem repeat region, with domain 1 of ICAM1 is implicated in
CC cell migration and metastases. Isoform 1 binds directly the SH2 domain
CC of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling.
CC The cytoplasmic tail (MUC1CT) interacts with several proteins such as
CC SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases
CC interaction with GSK3B. Interacts with CTNNB1/beta-catenin and
CC JUP/gamma-catenin and promotes cell adhesion. Interaction with
CC JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3
CC and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and,
CC to a much lesser extent, the interaction with ERBB3 and ERBB4.
CC Interacts with P53 in response to DNA damage. Interacts with KLF4.
CC Interacts with estrogen receptor alpha/ESR1, through its DNA-binding
CC domain, and stimulates its transcription activity. Binds ADAM17.
CC Isoform ZD forms disulfide-linked oligomers.
CC {ECO:0000269|PubMed:11152665, ECO:0000269|PubMed:11173916,
CC ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11877440,
CC ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:12750561,
CC ECO:0000269|PubMed:12832415, ECO:0000269|PubMed:12939402,
CC ECO:0000269|PubMed:14688481, ECO:0000269|PubMed:15471854,
CC ECO:0000269|PubMed:15513966, ECO:0000269|PubMed:15710329,
CC ECO:0000269|PubMed:16288032, ECO:0000269|PubMed:16427018,
CC ECO:0000269|PubMed:16507569, ECO:0000269|PubMed:16983337,
CC ECO:0000269|PubMed:17308127, ECO:0000269|PubMed:17524503,
CC ECO:0000269|PubMed:7664271, ECO:0000269|PubMed:9139698,
CC ECO:0000269|PubMed:9819408}.
CC -!- INTERACTION:
CC P15941; P00519: ABL1; NbExp=8; IntAct=EBI-2804728, EBI-375543;
CC P15941; P00533: EGFR; NbExp=4; IntAct=EBI-2804728, EBI-297353;
CC P15941; P08581: MET; NbExp=2; IntAct=EBI-2804728, EBI-1039152;
CC P15941; P15941-7: MUC1; NbExp=2; IntAct=EBI-2804728, EBI-4396776;
CC P15941-11; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-17263240, EBI-10225815;
CC P15941-11; O60242: ADGRB3; NbExp=3; IntAct=EBI-17263240, EBI-2682765;
CC P15941-11; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-17263240, EBI-10827839;
CC P15941-11; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-17263240, EBI-12109402;
CC P15941-11; P02652: APOA2; NbExp=3; IntAct=EBI-17263240, EBI-1171525;
CC P15941-11; P05067-2: APP; NbExp=3; IntAct=EBI-17263240, EBI-17264467;
CC P15941-11; P29972: AQP1; NbExp=3; IntAct=EBI-17263240, EBI-745213;
CC P15941-11; P41181: AQP2; NbExp=3; IntAct=EBI-17263240, EBI-12701138;
CC P15941-11; Q92482: AQP3; NbExp=3; IntAct=EBI-17263240, EBI-2808854;
CC P15941-11; Q9H2C2: ARV1; NbExp=3; IntAct=EBI-17263240, EBI-11724186;
CC P15941-11; Q92843: BCL2L2; NbExp=3; IntAct=EBI-17263240, EBI-707714;
CC P15941-11; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-17263240, EBI-12244618;
CC P15941-11; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-17263240, EBI-8648738;
CC P15941-11; P06681: C2; NbExp=3; IntAct=EBI-17263240, EBI-2835920;
CC P15941-11; O14523: C2CD2L; NbExp=3; IntAct=EBI-17263240, EBI-12822627;
CC P15941-11; Q06432: CACNG1; NbExp=3; IntAct=EBI-17263240, EBI-9686780;
CC P15941-11; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-17263240, EBI-9083477;
CC P15941-11; Q08722-3: CD47; NbExp=3; IntAct=EBI-17263240, EBI-17263290;
CC P15941-11; P19397: CD53; NbExp=3; IntAct=EBI-17263240, EBI-6657396;
CC P15941-11; P34810: CD68; NbExp=3; IntAct=EBI-17263240, EBI-2826276;
CC P15941-11; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-17263240, EBI-12256978;
CC P15941-11; P56747: CLDN6; NbExp=3; IntAct=EBI-17263240, EBI-12955011;
CC P15941-11; Q8NHS1: CLDND2; NbExp=3; IntAct=EBI-17263240, EBI-11959453;
CC P15941-11; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-17263240, EBI-2807956;
CC P15941-11; Q4VAQ0: COL8A2; NbExp=3; IntAct=EBI-17263240, EBI-10241815;
CC P15941-11; Q8N6G5: CSGALNACT2; NbExp=3; IntAct=EBI-17263240, EBI-10267100;
CC P15941-11; Q07325: CXCL9; NbExp=3; IntAct=EBI-17263240, EBI-3911467;
CC P15941-11; O43169: CYB5B; NbExp=3; IntAct=EBI-17263240, EBI-1058710;
CC P15941-11; P78329: CYP4F2; NbExp=3; IntAct=EBI-17263240, EBI-1752413;
CC P15941-11; P56851: EDDM3B; NbExp=3; IntAct=EBI-17263240, EBI-10215665;
CC P15941-11; Q9BV81: EMC6; NbExp=3; IntAct=EBI-17263240, EBI-2820492;
CC P15941-11; P54852: EMP3; NbExp=3; IntAct=EBI-17263240, EBI-3907816;
CC P15941-11; O75355-2: ENTPD3; NbExp=3; IntAct=EBI-17263240, EBI-12279764;
CC P15941-11; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-17263240, EBI-711490;
CC P15941-11; P01350: GAST; NbExp=3; IntAct=EBI-17263240, EBI-3436637;
CC P15941-11; P39905-3: GDNF; NbExp=3; IntAct=EBI-17263240, EBI-12702062;
CC P15941-11; Q9Y3E0: GOLT1B; NbExp=3; IntAct=EBI-17263240, EBI-4402607;
CC P15941-11; Q9NPR9: GPR108; NbExp=3; IntAct=EBI-17263240, EBI-11343451;
CC P15941-11; Q9HCP6: HHATL; NbExp=3; IntAct=EBI-17263240, EBI-5916693;
CC P15941-11; O60725: ICMT; NbExp=3; IntAct=EBI-17263240, EBI-11721771;
CC P15941-11; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-17263240, EBI-8503746;
CC P15941-11; P11215: ITGAM; NbExp=3; IntAct=EBI-17263240, EBI-2568251;
CC P15941-11; Q969L2: MAL2; NbExp=3; IntAct=EBI-17263240, EBI-944295;
CC P15941-11; Q13021: MALL; NbExp=3; IntAct=EBI-17263240, EBI-750078;
CC P15941-11; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-17263240, EBI-10317612;
CC P15941-11; Q6N075: MFSD5; NbExp=3; IntAct=EBI-17263240, EBI-3920969;
CC P15941-11; P30301: MIP; NbExp=3; IntAct=EBI-17263240, EBI-8449636;
CC P15941-11; Q96S97: MYADM; NbExp=3; IntAct=EBI-17263240, EBI-13301517;
CC P15941-11; O95167: NDUFA3; NbExp=3; IntAct=EBI-17263240, EBI-1246131;
CC P15941-11; Q99519: NEU1; NbExp=3; IntAct=EBI-17263240, EBI-721517;
CC P15941-11; Q92982: NINJ1; NbExp=3; IntAct=EBI-17263240, EBI-2802124;
CC P15941-11; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-17263240, EBI-10317425;
CC P15941-11; Q16617: NKG7; NbExp=3; IntAct=EBI-17263240, EBI-3919611;
CC P15941-11; Q8N912: NRAC; NbExp=3; IntAct=EBI-17263240, EBI-12051377;
CC P15941-11; Q8NH19: OR10AG1; NbExp=3; IntAct=EBI-17263240, EBI-13339917;
CC P15941-11; Q6TCH4: PAQR6; NbExp=3; IntAct=EBI-17263240, EBI-17265310;
CC P15941-11; P26678: PLN; NbExp=3; IntAct=EBI-17263240, EBI-692836;
CC P15941-11; P60201-2: PLP1; NbExp=3; IntAct=EBI-17263240, EBI-12188331;
CC P15941-11; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-17263240, EBI-11721828;
CC P15941-11; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-17263240, EBI-8652812;
CC P15941-11; Q59EV6: PPGB; NbExp=3; IntAct=EBI-17263240, EBI-14210385;
CC P15941-11; P30405: PPIF; NbExp=3; IntAct=EBI-17263240, EBI-5544229;
CC P15941-11; Q96AA3: RFT1; NbExp=3; IntAct=EBI-17263240, EBI-6269616;
CC P15941-11; Q02161-2: RHD; NbExp=3; IntAct=EBI-17263240, EBI-17249212;
CC P15941-11; Q8TAC9: SCAMP5; NbExp=3; IntAct=EBI-17263240, EBI-2695784;
CC P15941-11; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-17263240, EBI-9679163;
CC P15941-11; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-17263240, EBI-749270;
CC P15941-11; P11686: SFTPC; NbExp=3; IntAct=EBI-17263240, EBI-10197617;
CC P15941-11; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-17263240, EBI-10262251;
CC P15941-11; Q969S0: SLC35B4; NbExp=3; IntAct=EBI-17263240, EBI-10281213;
CC P15941-11; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-17263240, EBI-12867720;
CC P15941-11; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-17263240, EBI-10314552;
CC P15941-11; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-17263240, EBI-8640191;
CC P15941-11; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-17263240, EBI-12188413;
CC P15941-11; Q9NZ01: TECR; NbExp=3; IntAct=EBI-17263240, EBI-2877718;
CC P15941-11; P07204: THBD; NbExp=3; IntAct=EBI-17263240, EBI-941422;
CC P15941-11; Q9BZW4: TM6SF2; NbExp=3; IntAct=EBI-17263240, EBI-13082040;
CC P15941-11; P17152: TMEM11; NbExp=3; IntAct=EBI-17263240, EBI-723946;
CC P15941-11; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-17263240, EBI-10171534;
CC P15941-11; Q9BTD3: TMEM121; NbExp=3; IntAct=EBI-17263240, EBI-12155101;
CC P15941-11; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-17263240, EBI-10694905;
CC P15941-11; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-17263240, EBI-348587;
CC P15941-11; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-17263240, EBI-2800360;
CC P15941-11; Q9P0S9: TMEM14C; NbExp=3; IntAct=EBI-17263240, EBI-2339195;
CC P15941-11; Q14656: TMEM187; NbExp=3; IntAct=EBI-17263240, EBI-13046724;
CC P15941-11; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-17263240, EBI-12195227;
CC P15941-11; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-17263240, EBI-12887458;
CC P15941-11; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-17263240, EBI-12015604;
CC P15941-11; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-17263240, EBI-2548832;
CC P15941-11; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-17263240, EBI-12111910;
CC P15941-11; Q9Y2Y6: TMEM98; NbExp=3; IntAct=EBI-17263240, EBI-7333781;
CC P15941-11; O14763: TNFRSF10B; NbExp=3; IntAct=EBI-17263240, EBI-518882;
CC P15941-11; Q8N609: TRAM1L1; NbExp=3; IntAct=EBI-17263240, EBI-11996766;
CC P15941-11; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-17263240, EBI-10243654;
CC P15941-11; Q53HI1: UNC50; NbExp=3; IntAct=EBI-17263240, EBI-7601760;
CC P15941-11; O95183: VAMP5; NbExp=3; IntAct=EBI-17263240, EBI-10191195;
CC P15941-11; Q9BQB6: VKORC1; NbExp=3; IntAct=EBI-17263240, EBI-6256462;
CC P15941-11; Q8IVQ6: ZDHHC21; NbExp=3; IntAct=EBI-17263240, EBI-2849773;
CC PRO_0000317447; P17676: CEBPB; NbExp=8; IntAct=EBI-10053698, EBI-969696;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:11118479, ECO:0000269|PubMed:12832415,
CC ECO:0000269|PubMed:12939402, ECO:0000269|PubMed:15471854,
CC ECO:0000269|PubMed:15972891, ECO:0000269|PubMed:16507569,
CC ECO:0000269|PubMed:17524503, ECO:0000269|PubMed:17545600}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:11118479,
CC ECO:0000269|PubMed:12832415, ECO:0000269|PubMed:12939402,
CC ECO:0000269|PubMed:15471854, ECO:0000269|PubMed:15972891,
CC ECO:0000269|PubMed:16507569, ECO:0000269|PubMed:17524503,
CC ECO:0000269|PubMed:17545600}. Note=Exclusively located in the apical
CC domain of the plasma membrane of highly polarized epithelial cells.
CC After endocytosis, internalized and recycled to the cell membrane.
CC Located to microvilli and to the tips of long filopodial protusions.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform Y]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 9]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Mucin-1 subunit beta]: Cell membrane. Cytoplasm.
CC Nucleus. Note=On EGF and PDGFRB stimulation, transported to the nucleus
CC through interaction with CTNNB1, a process which is stimulated by
CC phosphorylation. On HRG stimulation, colocalizes with JUP/gamma-catenin
CC at the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=17;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=A;
CC IsoId=P15941-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P15941-2; Sequence=VSP_003280;
CC Name=3; Synonyms=C;
CC IsoId=P15941-3; Sequence=VSP_003281;
CC Name=4; Synonyms=D;
CC IsoId=P15941-4; Sequence=VSP_003282;
CC Name=5; Synonyms=SEC;
CC IsoId=P15941-5; Sequence=VSP_003288, VSP_003289;
CC Name=6; Synonyms=X;
CC IsoId=P15941-6; Sequence=VSP_003283, VSP_003284;
CC Name=Y; Synonyms=MUC1/Y;
CC IsoId=P15941-7; Sequence=VSP_003285;
CC Name=8; Synonyms=Z;
CC IsoId=P15941-8; Sequence=VSP_003286;
CC Name=9; Synonyms=S;
CC IsoId=P15941-9; Sequence=VSP_003286, VSP_003287;
CC Name=F;
CC IsoId=P15941-10; Sequence=VSP_035046, VSP_035047;
CC Name=Y-LSP;
CC IsoId=P15941-11; Sequence=VSP_003280, VSP_003285;
CC Name=S2;
CC IsoId=P15941-12; Sequence=VSP_003280, VSP_003285, VSP_003287;
CC Name=M6;
CC IsoId=P15941-13; Sequence=VSP_003286, VSP_046962, VSP_046963;
CC Name=ZD; Synonyms=J19;
CC IsoId=P15941-14; Sequence=VSP_047575, VSP_047576;
CC Name=T10;
CC IsoId=P15941-15; Sequence=VSP_003280, VSP_047873;
CC Name=E2;
CC IsoId=P15941-16; Sequence=VSP_003280, VSP_047872;
CC Name=J13;
CC IsoId=P15941-17; Sequence=VSP_003280, VSP_003285, VSP_047874;
CC -!- TISSUE SPECIFICITY: Expressed on the apical surface of epithelial
CC cells, especially of airway passages, breast and uterus. Also expressed
CC in activated and unactivated T-cells. Overexpressed in epithelial
CC tumors, such as breast or ovarian cancer and also in non-epithelial
CC tumor cells. Isoform Y is expressed in tumor cells only.
CC {ECO:0000269|PubMed:15513966, ECO:0000269|PubMed:9212228}.
CC -!- DEVELOPMENTAL STAGE: During fetal development, expressed at low levels
CC in the colonic epithelium from 13 weeks of gestation.
CC {ECO:0000269|PubMed:9536947}.
CC -!- PTM: Highly glycosylated (N- and O-linked carbohydrates and sialic
CC acid). O-glycosylated to a varying degree on serine and threonine
CC residues within each tandem repeat, ranging from mono- to penta-
CC glycosylation. The average density ranges from about 50% in human milk
CC to over 90% in T47D breast cancer cells. Further sialylation occurs
CC during recycling. Membrane-shed glycoproteins from kidney and breast
CC cancer cells have preferentially sialyated core 1 structures, while
CC secreted forms from the same tissues display mainly core 2 structures.
CC The O-glycosylated content is overlapping in both these tissues with
CC terminal fucose and galactose, 2- and 3-linked galactose, 3- and 3,6-
CC linked GalNAc-ol and 4-linked GlcNAc predominating. Differentially O-
CC glycosylated in breast carcinomas with 3,4-linked GlcNAc. N-
CC glycosylation consists of high-mannose, acidic complex-type and hybrid
CC glycans in the secreted form MUC1/SEC, and neutral complex-type in the
CC transmembrane form, MUC1/TM. {ECO:0000269|PubMed:10373415,
CC ECO:0000269|PubMed:7744025, ECO:0000269|PubMed:9312074,
CC ECO:0000269|PubMed:9597769}.
CC -!- PTM: Proteolytic cleavage in the SEA domain occurs in the endoplasmic
CC reticulum by an autoproteolytic mechanism and requires the full-length
CC SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1
CC site. Cleavage at this site also occurs on isoform MUC1/X but not on
CC isoform MUC1/Y. Ectodomain shedding is mediated by ADAM17.
CC {ECO:0000269|PubMed:11341784, ECO:0000269|PubMed:12441351,
CC ECO:0000269|PubMed:15987679}.
CC -!- PTM: Dual palmitoylation on cysteine residues in the CQC motif is
CC required for recycling from endosomes back to the plasma membrane.
CC {ECO:0000269|PubMed:16507569}.
CC -!- PTM: Phosphorylated on tyrosines and serine residues in the C-terminal.
CC Phosphorylation on tyrosines in the C-terminal increases the nuclear
CC location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces
CC binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation
CC of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation
CC inhibits interaction with GSK3B. Src- and EGFR-mediated phosphorylation
CC on Tyr-1229 increases binding to beta-catenin/CTNNB1. GSK3B-mediated
CC phosphorylation on Ser-1227 decreases this interaction but restores the
CC formation of the beta-cadherin/E-cadherin complex. On T-cell receptor
CC activation, phosphorylated by LCK. PDGFR-mediated phosphorylation
CC increases nuclear colocalization of MUC1CT and CTNNB1.
CC {ECO:0000269|PubMed:11152665, ECO:0000269|PubMed:11483589,
CC ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12750561,
CC ECO:0000269|PubMed:14521915, ECO:0000269|PubMed:15513966,
CC ECO:0000269|PubMed:16288032, ECO:0000269|PubMed:17545600,
CC ECO:0000269|PubMed:7664271, ECO:0000269|PubMed:7988707,
CC ECO:0000269|PubMed:9819408}.
CC -!- PTM: The N-terminal sequence has been shown to begin at position 24 or
CC 28. {ECO:0000269|PubMed:11341784}.
CC -!- POLYMORPHISM: The number of repeats is highly polymorphic. It varies
CC from 21 to 125 in the northern European population. The most frequent
CC alleles contains 41 and 85 repeats. The tandemly repeated icosapeptide
CC underlies polymorphism at three positions:
CC PAPGSTAP[PAQT]AHGVTSAP[DT/ES]R, DT -> ES and the single replacements P
CC -> A, P -> Q and P-> T. The most frequent replacement DT -> ES occurs
CC in up to 50% of the repeats.
CC -!- DISEASE: Note=MUC1/CA 15-3 is used as a serological clinical marker of
CC breast cancer to monitor response to breast cancer treatment and
CC disease recurrence (PubMed:20816948). Decreased levels over time may be
CC indicative of a positive response to treatment. Conversely, increased
CC levels may indicate disease progression. At an early stage disease,
CC only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA
CC 15-3 is not a useful screening test. Most antibodies target the highly
CC immunodominant core peptide domain of 20 amino acid
CC (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize
CC glycosylated epitopes. {ECO:0000269|PubMed:20816948}.
CC -!- DISEASE: Tubulointerstitial kidney disease, autosomal dominant, 2
CC (ADTKD2) [MIM:174000]: A form of autosomal dominant tubulointerstitial
CC kidney disease, a genetically heterogeneous disorder characterized by
CC slowly progressive loss of kidney function, bland urinary sediment,
CC hyperuricemia, absent or mildly increased albuminuria, lack of severe
CC hypertension during the early stages, and normal or small kidneys on
CC ultrasound. Renal histology shows variable abnormalities including
CC interstitial fibrosis with tubular atrophy, microcystic dilatation of
CC the tubules, thickening of tubular basement membranes, medullary cysts,
CC and secondary glomerulosclerotic or glomerulocystic changes with
CC abnormal glomerular tufting. There is significant variability, as well
CC as incomplete penetrance. {ECO:0000269|PubMed:23396133}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The name KL-6 was originally that of a murine monoclonal
CC antibody reacting with pulmonary adenocarcinoma cell lines and
CC pulmonary epithelial cells. This antibody recognizes a sialylated
CC carbohydrate chain on MUC1.
CC -!- MISCELLANEOUS: [Isoform Y-LSP]: Lacks the mucin repeats. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform ZD]: Lacks the mucin repeats. Exists as a
CC disulfide-linked oligomer. {ECO:0000305}.
CC -!- CAUTION: O-glycosylation sites are annotated in first sequence repeat
CC only. Residues at similar position are probably glycosylated in all
CC repeats. Experimental sites were determined in a synthetic peptide
CC glycosylated in vitro (PubMed:7744025, PubMed:9597769).
CC {ECO:0000305|PubMed:7744025, ECO:0000305|PubMed:9597769}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD14369.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD14376.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mucin database;
CC URL="http://www.medkem.gu.se/mucinbiology/databases/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/muc1/";
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DR EMBL; J05582; AAA60019.1; -; mRNA.
DR EMBL; M32738; AAA35804.1; -; mRNA.
DR EMBL; M32739; AAA35806.1; -; mRNA.
DR EMBL; M34089; AAA35807.1; -; mRNA.
DR EMBL; M34088; AAA35805.1; -; mRNA.
DR EMBL; J05581; AAA59876.1; -; mRNA.
DR EMBL; M61170; AAB53150.1; -; Genomic_DNA.
DR EMBL; X52229; CAA36478.1; ALT_SEQ; mRNA.
DR EMBL; X52228; CAA36477.1; ALT_SEQ; mRNA.
DR EMBL; M35093; AAB59612.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X80761; CAA56734.1; -; mRNA.
DR EMBL; U60259; AAD10856.1; -; mRNA.
DR EMBL; U60260; AAD10857.1; -; mRNA.
DR EMBL; U60261; AAD10858.1; -; mRNA.
DR EMBL; AF125525; AAD27842.1; -; mRNA.
DR EMBL; AY466157; AAR28764.1; -; mRNA.
DR EMBL; AY327582; AAP97013.1; -; mRNA.
DR EMBL; AY327584; AAP97015.1; -; mRNA.
DR EMBL; AY327586; AAP97017.1; -; mRNA.
DR EMBL; AY327587; AAP97018.1; -; mRNA.
DR EMBL; EF583653; ABQ59628.1; -; mRNA.
DR EMBL; EF670711; ABS01298.1; -; mRNA.
DR EMBL; EF670712; ABS01299.1; -; mRNA.
DR EMBL; FJ226040; ACI25172.1; -; mRNA.
DR EMBL; FJ226047; ACI25179.1; -; mRNA.
DR EMBL; AF348143; AAK30142.1; -; mRNA.
DR EMBL; AY463543; AAR18816.1; -; Genomic_DNA.
DR EMBL; AL713999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53116.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53117.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53118.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53119.1; -; Genomic_DNA.
DR EMBL; BC120974; AAI20975.1; -; mRNA.
DR EMBL; BC120975; AAI20976.1; -; mRNA.
DR EMBL; Z17324; CAA78972.1; -; mRNA.
DR EMBL; Z17325; CAA78973.1; -; mRNA.
DR EMBL; M31823; AAA35757.1; -; mRNA.
DR EMBL; S81781; AAD14376.1; ALT_INIT; mRNA.
DR EMBL; S81736; AAD14369.1; ALT_INIT; mRNA.
DR EMBL; M21868; AAA59874.1; ALT_SEQ; mRNA.
DR CCDS; CCDS1098.1; -. [P15941-8]
DR CCDS; CCDS30882.1; -. [P15941-11]
DR CCDS; CCDS30883.1; -. [P15941-7]
DR CCDS; CCDS41408.1; -. [P15941-12]
DR CCDS; CCDS41409.1; -. [P15941-10]
DR CCDS; CCDS55641.1; -. [P15941-6]
DR CCDS; CCDS55642.1; -. [P15941-13]
DR PIR; A35175; A35175.
DR RefSeq; NP_001018016.1; NM_001018016.2. [P15941-11]
DR RefSeq; NP_001018017.1; NM_001018017.2. [P15941-7]
DR RefSeq; NP_001037855.1; NM_001044390.2. [P15941-10]
DR RefSeq; NP_001037856.1; NM_001044391.2.
DR RefSeq; NP_001037857.1; NM_001044392.2. [P15941-12]
DR RefSeq; NP_001037858.1; NM_001044393.2.
DR RefSeq; NP_001191214.1; NM_001204285.1.
DR RefSeq; NP_001191215.1; NM_001204286.1.
DR RefSeq; NP_001191216.1; NM_001204287.1.
DR RefSeq; NP_001191217.1; NM_001204288.1.
DR RefSeq; NP_001191218.1; NM_001204289.1.
DR RefSeq; NP_001191219.1; NM_001204290.1.
DR RefSeq; NP_001191220.1; NM_001204291.1.
DR RefSeq; NP_001191221.1; NM_001204292.1.
DR RefSeq; NP_001191222.1; NM_001204293.1. [P15941-13]
DR RefSeq; NP_001191223.1; NM_001204294.1. [P15941-6]
DR RefSeq; NP_001191224.1; NM_001204295.1.
DR RefSeq; NP_001191225.1; NM_001204296.1.
DR RefSeq; NP_001191226.1; NM_001204297.1.
DR RefSeq; NP_002447.4; NM_002456.5. [P15941-8]
DR PDB; 1SM3; X-ray; 1.95 A; P=919-931.
DR PDB; 2ACM; NMR; -; A=1042-1097, B=1098-1152.
DR PDB; 2FO4; X-ray; 2.70 A; P=140-146.
DR PDB; 5T6P; X-ray; 1.97 A; E/F=921-928.
DR PDB; 5T78; X-ray; 2.20 A; E/F=921-928.
DR PDB; 6FZQ; X-ray; 1.70 A; P=921-926.
DR PDB; 6FZR; X-ray; 1.80 A; P=921-926.
DR PDB; 6KX1; X-ray; 1.77 A; C=918-932.
DR PDB; 6TGG; X-ray; 2.00 A; P=921-926.
DR PDB; 7Q4I; X-ray; 2.40 A; F/G=921-926.
DR PDBsum; 1SM3; -.
DR PDBsum; 2ACM; -.
DR PDBsum; 2FO4; -.
DR PDBsum; 5T6P; -.
DR PDBsum; 5T78; -.
DR PDBsum; 6FZQ; -.
DR PDBsum; 6FZR; -.
DR PDBsum; 6KX1; -.
DR PDBsum; 6TGG; -.
DR PDBsum; 7Q4I; -.
DR AlphaFoldDB; P15941; -.
DR SMR; P15941; -.
DR BioGRID; 110669; 158.
DR DIP; DIP-41890N; -.
DR IntAct; P15941; 121.
DR MINT; P15941; -.
DR STRING; 9606.ENSP00000484824; -.
DR ChEMBL; CHEMBL3580494; -.
DR DrugBank; DB11090; Potassium nitrate.
DR DrugBank; DB06584; TG4010.
DR MEROPS; S71.001; -.
DR GlyConnect; 372; 9 O-Linked glycans.
DR GlyConnect; 373; 8 O-Linked glycans.
DR GlyConnect; 374; 7 N-Linked glycans (3 sites), 8 O-Linked glycans.
DR GlyConnect; 375; 10 O-Linked glycans.
DR GlyConnect; 376; 10 O-Linked glycans.
DR GlyConnect; 377; 7 O-Linked glycans.
DR GlyConnect; 413; 5 N-Linked glycans (1 site), 14 O-Linked glycans.
DR GlyGen; P15941; 15 sites, 5 N-linked glycans (1 site), 38 O-linked glycans (8 sites).
DR iPTMnet; P15941; -.
DR PhosphoSitePlus; P15941; -.
DR SwissPalm; P15941; -.
DR BioMuta; MUC1; -.
DR DMDM; 296439295; -.
DR CPTAC; CPTAC-146; -.
DR CPTAC; CPTAC-147; -.
DR CPTAC; CPTAC-719; -.
DR CPTAC; CPTAC-730; -.
DR EPD; P15941; -.
DR jPOST; P15941; -.
DR MassIVE; P15941; -.
DR MaxQB; P15941; -.
DR PaxDb; P15941; -.
DR PeptideAtlas; P15941; -.
DR PRIDE; P15941; -.
DR ProteomicsDB; 1779; -.
DR ProteomicsDB; 53249; -. [P15941-1]
DR ProteomicsDB; 53250; -. [P15941-10]
DR ProteomicsDB; 53251; -. [P15941-2]
DR ProteomicsDB; 53252; -. [P15941-3]
DR ProteomicsDB; 53253; -. [P15941-4]
DR ProteomicsDB; 53254; -. [P15941-5]
DR ProteomicsDB; 53255; -. [P15941-6]
DR ProteomicsDB; 53256; -. [P15941-7]
DR ProteomicsDB; 53257; -. [P15941-8]
DR ProteomicsDB; 53258; -. [P15941-9]
DR ProteomicsDB; 58806; -.
DR ProteomicsDB; 6245; -.
DR ProteomicsDB; 69255; -.
DR ProteomicsDB; 69256; -.
DR ProteomicsDB; 767; -.
DR ABCD; P15941; 33 sequenced antibodies.
DR Antibodypedia; 1298; 4509 antibodies from 54 providers.
DR CPTC; P15941; 2 antibodies.
DR DNASU; 4582; -.
DR Ensembl; ENST00000337604.6; ENSP00000338983.5; ENSG00000185499.17. [P15941-8]
DR Ensembl; ENST00000342482.8; ENSP00000342814.4; ENSG00000185499.17. [P15941-16]
DR Ensembl; ENST00000343256.9; ENSP00000339690.5; ENSG00000185499.17. [P15941-10]
DR Ensembl; ENST00000368389.6; ENSP00000357374.2; ENSG00000185499.17. [P15941-9]
DR Ensembl; ENST00000368390.7; ENSP00000357375.3; ENSG00000185499.17. [P15941-7]
DR Ensembl; ENST00000368392.7; ENSP00000357377.3; ENSG00000185499.17. [P15941-11]
DR Ensembl; ENST00000368393.7; ENSP00000357378.3; ENSG00000185499.17. [P15941-13]
DR Ensembl; ENST00000368396.8; ENSP00000357381.4; ENSG00000185499.17. [P15941-12]
DR Ensembl; ENST00000368398.7; ENSP00000357383.3; ENSG00000185499.17. [P15941-6]
DR GeneID; 4582; -.
DR KEGG; hsa:4582; -.
DR UCSC; uc001fia.4; human. [P15941-1]
DR CTD; 4582; -.
DR DisGeNET; 4582; -.
DR GeneCards; MUC1; -.
DR GeneReviews; MUC1; -.
DR HGNC; HGNC:7508; MUC1.
DR HPA; ENSG00000185499; Tissue enhanced (kidney, stomach).
DR MalaCards; MUC1; -.
DR MIM; 113720; gene.
DR MIM; 158340; gene.
DR MIM; 174000; phenotype.
DR neXtProt; NX_P15941; -.
DR OpenTargets; ENSG00000185499; -.
DR Orphanet; 88949; MUC1-related autosomal dominant tubulointerstitial kidney disease.
DR PharmGKB; PA31309; -.
DR VEuPathDB; HostDB:ENSG00000185499; -.
DR eggNOG; ENOG502QWCT; Eukaryota.
DR GeneTree; ENSGT00710000106874; -.
DR HOGENOM; CLU_1386987_0_0_1; -.
DR InParanoid; P15941; -.
DR OrthoDB; 945460at2759; -.
DR PhylomeDB; P15941; -.
DR PathwayCommons; P15941; -.
DR Reactome; R-HSA-5083625; Defective GALNT3 causes HFTC.
DR Reactome; R-HSA-5083632; Defective C1GALT1C1 causes TNPS.
DR Reactome; R-HSA-5083636; Defective GALNT12 causes CRCS1.
DR Reactome; R-HSA-5621480; Dectin-2 family.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-913709; O-linked glycosylation of mucins.
DR Reactome; R-HSA-977068; Termination of O-glycan biosynthesis.
DR SignaLink; P15941; -.
DR SIGNOR; P15941; -.
DR BioGRID-ORCS; 4582; 14 hits in 1082 CRISPR screens.
DR ChiTaRS; MUC1; human.
DR EvolutionaryTrace; P15941; -.
DR GeneWiki; MUC1; -.
DR GenomeRNAi; 4582; -.
DR Pharos; P15941; Tchem.
DR PRO; PR:P15941; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P15941; protein.
DR Bgee; ENSG00000185499; Expressed in pylorus and 170 other tissues.
DR ExpressionAtlas; P15941; baseline and differential.
DR Genevisible; P15941; HS.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0031982; C:vesicle; HDA:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:BHF-UCL.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IDA:BHF-UCL.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:BHF-UCL.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; IDA:CACAO.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0090240; P:positive regulation of histone H4 acetylation; IDA:BHF-UCL.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IDA:BHF-UCL.
DR GO; GO:0043618; P:regulation of transcription from RNA polymerase II promoter in response to stress; IDA:BHF-UCL.
DR DisProt; DP01790; -.
DR Gene3D; 6.10.140.600; -; 1.
DR IDEAL; IID00195; -.
DR InterPro; IPR000082; SEA_dom.
DR InterPro; IPR036364; SEA_dom_sf.
DR Pfam; PF01390; SEA; 1.
DR SMART; SM00200; SEA; 1.
DR SUPFAM; SSF82671; SSF82671; 1.
DR PROSITE; PS50024; SEA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW Cytoplasm; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Lipoprotein; Membrane; Nucleus; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix; Tumor suppressor.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:10373415,
FT ECO:0000269|PubMed:11341784"
FT CHAIN 24..1255
FT /note="Mucin-1"
FT /id="PRO_0000019277"
FT CHAIN 24..1097
FT /note="Mucin-1 subunit alpha"
FT /id="PRO_0000317446"
FT CHAIN 1098..1255
FT /note="Mucin-1 subunit beta"
FT /id="PRO_0000317447"
FT TOPO_DOM 24..1158
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1159..1181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1182..1255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 61..80
FT /note="1; approximate"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 81..100
FT /note="2; approximate"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 101..120
FT /note="3"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 121..140
FT /note="4"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 141..160
FT /note="5"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 161..180
FT /note="6"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 181..200
FT /note="7"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 201..220
FT /note="8"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 221..240
FT /note="9"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 241..260
FT /note="10"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 261..280
FT /note="11"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 281..300
FT /note="12"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 301..320
FT /note="13"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 321..340
FT /note="14"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 341..360
FT /note="15"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 361..380
FT /note="16"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 381..400
FT /note="17"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 401..420
FT /note="18"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 421..440
FT /note="19"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 441..460
FT /note="20"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 461..480
FT /note="21"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 481..500
FT /note="22"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 501..520
FT /note="23"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 521..540
FT /note="24"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 541..560
FT /note="25"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 561..580
FT /note="26"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 581..600
FT /note="27"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 601..620
FT /note="28"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 621..640
FT /note="29"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 641..660
FT /note="30"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 661..680
FT /note="31"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 681..700
FT /note="32"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 701..720
FT /note="33"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 721..740
FT /note="34"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 741..760
FT /note="35"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 761..780
FT /note="36"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 781..800
FT /note="37"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 801..820
FT /note="38"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 821..840
FT /note="39"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 841..860
FT /note="40"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 861..880
FT /note="41"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 881..900
FT /note="42"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 901..920
FT /note="43"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 921..940
FT /note="44"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 941..960
FT /note="45"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 961..980
FT /note="46; approximate"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 981..1000
FT /note="47; approximate"
FT /evidence="ECO:0000269|PubMed:11350974"
FT REPEAT 1001..1020
FT /note="48; approximate"
FT /evidence="ECO:0000269|PubMed:11350974"
FT DOMAIN 1039..1148
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT REGION 23..1033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..965
FT /note="42 X 20 AA approximate tandem repeats of P-A-P-G-S-
FT T-A-P-P-A-H-G-V-T-S-A-P-D-T-R"
FT REGION 1192..1228
FT /note="Interaction with P53"
FT REGION 1214..1237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1223..1230
FT /note="Required for interaction with GSK3B"
FT REGION 1233..1241
FT /note="Required for interaction with beta- and gamma-
FT catenins"
FT MOTIF 1203..1206
FT /note="Interaction with GRB2"
FT MOTIF 1229..1232
FT /note="Interaction with SRC and ESR1"
FT MOTIF 1243..1246
FT /note="Required for interaction with AP1S2"
FT COMPBIAS 23..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 953..1033
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1217..1237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1097..1098
FT /note="Cleavage; by autolysis"
FT MOD_RES 1203
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:14521915,
FT ECO:0000269|PubMed:17545600"
FT MOD_RES 1212
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:14521915"
FT MOD_RES 1218
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000269|PubMed:17545600"
FT MOD_RES 1224
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:11877440"
FT MOD_RES 1227
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:9819408,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1229
FT /note="Phosphotyrosine; by CSK, EGFR and SRC"
FT /evidence="ECO:0000269|PubMed:11152665,
FT ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:14521915,
FT ECO:0000269|PubMed:17545600"
FT MOD_RES 1243
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:14521915"
FT LIPID 1184
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:16507569"
FT LIPID 1186
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:16507569"
FT CARBOHYD 131
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:7744025,
FT ECO:0000305|PubMed:9597769"
FT CARBOHYD 139
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:7744025,
FT ECO:0000305|PubMed:9597769"
FT CARBOHYD 140
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 144
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 957
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 975
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1029
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1055
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 19..21
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.25"
FT /id="VSP_003281"
FT VAR_SEQ 19
FT /note="T -> TATTAPKPAT (in isoform 2, isoform Y-LSP,
FT isoform E2, isoform J13, isoform S2 and isoform T10)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:22941036, ECO:0000303|PubMed:2318825,
FT ECO:0000303|PubMed:2597151, ECO:0000303|PubMed:8608966,
FT ECO:0000303|Ref.15"
FT /id="VSP_003280"
FT VAR_SEQ 20..31
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.25"
FT /id="VSP_003282"
FT VAR_SEQ 54..1151
FT /note="Missing (in isoform E2)"
FT /evidence="ECO:0000303|PubMed:22941036"
FT /id="VSP_047872"
FT VAR_SEQ 54..1093
FT /note="Missing (in isoform T10)"
FT /evidence="ECO:0000303|PubMed:22941036"
FT /id="VSP_047873"
FT VAR_SEQ 54..1053
FT /note="Missing (in isoform J13, isoform Y, isoform Y-LSP
FT and isoform S2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15969018, ECO:0000303|PubMed:22941036,
FT ECO:0000303|PubMed:7925397, ECO:0000303|PubMed:9212228,
FT ECO:0000303|Ref.15"
FT /id="VSP_003285"
FT VAR_SEQ 54..1035
FT /note="Missing (in isoform 8, isoform 9 and isoform M6)"
FT /evidence="ECO:0000303|PubMed:22941036,
FT ECO:0000303|PubMed:9212228, ECO:0000303|Ref.12,
FT ECO:0000303|Ref.16"
FT /id="VSP_003286"
FT VAR_SEQ 54..96
FT /note="VSMTSSVLSSHSPGSGSSTTQGQDVTLAPATEPASGSAATWGQ -> IPAPT
FT TTKSCRETFLKCFCRFINKGVFWASPILSSGQDLWWYN (in isoform ZD)"
FT /evidence="ECO:0000303|PubMed:15623537,
FT ECO:0000303|PubMed:22941036"
FT /id="VSP_047575"
FT VAR_SEQ 54..87
FT /note="VSMTSSVLSSHSPGSGSSTTQGQDVTLAPATEPA -> IPAPTTTKSCRETF
FT LKCFCRFINKGVFWASPILS (in isoform F)"
FT /evidence="ECO:0000303|Ref.14"
FT /id="VSP_035046"
FT VAR_SEQ 54..70
FT /note="VSMTSSVLSSHSPGSGS -> IPAPTTTKSCRETFLKW (in isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:22941036,
FT ECO:0000303|PubMed:9212228"
FT /id="VSP_003283"
FT VAR_SEQ 71..1095
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:22941036,
FT ECO:0000303|PubMed:9212228"
FT /id="VSP_003284"
FT VAR_SEQ 88..1139
FT /note="Missing (in isoform F)"
FT /evidence="ECO:0000303|Ref.14"
FT /id="VSP_035047"
FT VAR_SEQ 97..1255
FT /note="Missing (in isoform ZD)"
FT /evidence="ECO:0000303|PubMed:15623537,
FT ECO:0000303|PubMed:22941036"
FT /id="VSP_047576"
FT VAR_SEQ 1077..1181
FT /note="Missing (in isoform 9 and isoform S2)"
FT /evidence="ECO:0000303|PubMed:22941036, ECO:0000303|Ref.12,
FT ECO:0000303|Ref.15"
FT /id="VSP_003287"
FT VAR_SEQ 1077..1087
FT /note="FLQIYKQGGFL -> VSIGLSFPMLP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:2351132"
FT /id="VSP_003288"
FT VAR_SEQ 1088..1255
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:2351132"
FT /id="VSP_003289"
FT VAR_SEQ 1141..1180
FT /note="VSDVPFPFSAQSGAGVPGWGIALLVLVCVLVALAIVYLIA -> GCLSVPPK
FT ELRAAGHLSSPGYLPSYERVPHLPHPWALCAP (in isoform M6)"
FT /evidence="ECO:0000303|PubMed:22941036, ECO:0000303|Ref.16"
FT /id="VSP_046962"
FT VAR_SEQ 1181..1255
FT /note="Missing (in isoform M6)"
FT /evidence="ECO:0000303|PubMed:22941036, ECO:0000303|Ref.16"
FT /id="VSP_046963"
FT VAR_SEQ 1232..1255
FT /note="VSAGNGGSSLSYTNPAVAATSANL -> RQNGWSTMPRGALPEESQG (in
FT isoform J13)"
FT /evidence="ECO:0000303|PubMed:22941036"
FT /id="VSP_047874"
FT VARIANT 1117
FT /note="V -> M (in dbSNP:rs1611770)"
FT /evidence="ECO:0000269|PubMed:15969018,
FT ECO:0000269|PubMed:22941036, ECO:0000269|Ref.17"
FT /id="VAR_019390"
FT VARIANT 1142
FT /note="S -> N (in dbSNP:rs11465207)"
FT /evidence="ECO:0000269|Ref.17"
FT /id="VAR_019391"
FT MUTAGEN 1098
FT /note="S->A,D,E,F,G,H,I,K,L,M,N,P,Q,R,V,W,Y: Completely
FT abrogates cleavage."
FT /evidence="ECO:0000269|PubMed:15987679"
FT MUTAGEN 1098
FT /note="S->C,T: Almost complete cleavage."
FT /evidence="ECO:0000269|PubMed:15987679"
FT MUTAGEN 1116
FT /note="D->A: Greatly reduced formation of isoform 5/isoform
FT Y complex."
FT /evidence="ECO:0000269|PubMed:10197628"
FT MUTAGEN 1116
FT /note="D->E: No effect on formation of isoform 5/isoform Y
FT complex."
FT /evidence="ECO:0000269|PubMed:10197628"
FT MUTAGEN 1184
FT /note="C->A: S-palmitoylation reduced by 50%. Complete loss
FT of palmitoylation, no effect on endocytosis, recycling
FT inhibited and AP1S1 binding reduced by 30%; when associated
FT with C-1186. Accumulates in intracellular compartments;
FT when associated with C-1186 and N-1203."
FT /evidence="ECO:0000269|PubMed:16507569"
FT MUTAGEN 1186
FT /note="C->A: S-palmitoylation reduced by 50%. Complete loss
FT of palmitoylation, no effect on endocytosis, recycling
FT inhibited, and AP1S1 binding reduced by 30%; when
FT associated with C-1184. Accumulates in intracellular
FT compartments; when associated with C-1184 and N-1203."
FT /evidence="ECO:0000269|PubMed:16507569"
FT MUTAGEN 1187..1189
FT /note="RRK->AAA: No nuclear targeting of HRG-stimulated
FT MUC1 C-terminal nor JUP/gamma-catenin. No effect on
FT interaction with JUP/gamma-catenin."
FT /evidence="ECO:0000269|PubMed:12939402,
FT ECO:0000269|PubMed:16507569"
FT MUTAGEN 1187..1189
FT /note="RRK->QQQ: No effect on palmitoylation."
FT /evidence="ECO:0000269|PubMed:12939402,
FT ECO:0000269|PubMed:16507569"
FT MUTAGEN 1191
FT /note="Y->F: No effect on EGFR-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:15471854"
FT MUTAGEN 1191
FT /note="Y->N: No effect on endocytosis."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:15471854"
FT MUTAGEN 1203
FT /note="Y->E: No effect on nuclear colocalization of MUC1CT
FT and CTNNB1. No effect on in vitro PDFGR-induced cell
FT invasiveness."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:15471854, ECO:0000269|PubMed:16507569,
FT ECO:0000269|PubMed:17545600"
FT MUTAGEN 1203
FT /note="Y->F: No effect on EGFR-mediated phosphorylation. No
FT nuclear localization of MUC1CT. Reduced in vitro PDGFR-
FT induced cell invasiveness."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:15471854, ECO:0000269|PubMed:16507569,
FT ECO:0000269|PubMed:17545600"
FT MUTAGEN 1203
FT /note="Y->N: Reduced endocytosis by 30%. Greatly reduced
FT binding to AP1S2 and GRB2. Binding AP1S1 reduced by 25%.
FT Reduced endocytosis by 77%; when associated with N-1243.
FT Accumulates in intracellular compartments; when associated
FT with C-1184 and C-1186."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:15471854, ECO:0000269|PubMed:16507569,
FT ECO:0000269|PubMed:17545600"
FT MUTAGEN 1209
FT /note="Y->F: Some reduction in EGFR-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11483589"
FT MUTAGEN 1218
FT /note="Y->F: No effect on EGFR-mediated phosphorylation. No
FT nuclear colocalization of MUC1CT and CTNNB1."
FT /evidence="ECO:0000269|PubMed:11483589,
FT ECO:0000269|PubMed:17545600"
FT MUTAGEN 1223
FT /note="S->A: No change in PRKCD- nor GSK3B-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11877440,
FT ECO:0000269|PubMed:9819408"
FT MUTAGEN 1224
FT /note="T->A: Loss of PRKCD-mediated phosphorylation.
FT Decreased PRKCD binding. No increased binding to CTNNB1 in
FT the presence of autophosphorylated PRKCD. Increases
FT formation of E-cadherin/beta-catenin complex."
FT /evidence="ECO:0000269|PubMed:11877440"
FT MUTAGEN 1227
FT /note="S->A: No change in PRKCD-mediated phosphorylation.
FT Loss of GSK3B-mediated phosphorylation. CTNNB1."
FT /evidence="ECO:0000269|PubMed:11877440,
FT ECO:0000269|PubMed:9819408"
FT MUTAGEN 1229
FT /note="Y->F: Greatly reduced EGFR- and Src-mediated
FT phosphorylation. No nuclear localization of MUC1CT. Reduced
FT in vitro PDGFR-mediated phosphorylation. Decreased Src-
FT binding."
FT /evidence="ECO:0000269|PubMed:11152665,
FT ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:14688481,
FT ECO:0000269|PubMed:15471854"
FT MUTAGEN 1229
FT /note="Y->N: No effect on endocytosis."
FT /evidence="ECO:0000269|PubMed:11152665,
FT ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:14688481,
FT ECO:0000269|PubMed:15471854"
FT MUTAGEN 1243
FT /note="Y->N: Reduces binding to AP1S2 by 33%. Greatly
FT reduced binding to GRB2. Reduced endocytosis by 50%.
FT Reduced endocytosis by 77%; when associated with N-1203."
FT /evidence="ECO:0000269|PubMed:15471854"
FT CONFLICT 2
FT /note="T -> A (in Ref. 24; AAD14369)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="P -> Q (in Ref. 22; AAA35757)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="P -> Q (in Ref. 22; AAA35757)"
FT /evidence="ECO:0000305"
FT CONFLICT 1021
FT /note="S -> T (in Ref. 2; AAA35805/AAA35807 and 3;
FT AAA59876)"
FT /evidence="ECO:0000305"
FT CONFLICT 1143
FT /note="D -> G (in Ref. 11; AAP97018)"
FT /evidence="ECO:0000305"
FT CONFLICT 1193
FT /note="Q -> L (in Ref. 13; AAK30142)"
FT /evidence="ECO:0000305"
FT CONFLICT 1231
FT /note="K -> T (in Ref. 9; AAD10858)"
FT /evidence="ECO:0000305"
FT CONFLICT 1251
FT /note="T -> A (in Ref. 1; AAA60019)"
FT /evidence="ECO:0000305"
FT STRAND 1042..1052
FT /evidence="ECO:0007829|PDB:2ACM"
FT HELIX 1056..1059
FT /evidence="ECO:0007829|PDB:2ACM"
FT HELIX 1064..1080
FT /evidence="ECO:0007829|PDB:2ACM"
FT TURN 1082..1085
FT /evidence="ECO:0007829|PDB:2ACM"
FT STRAND 1086..1096
FT /evidence="ECO:0007829|PDB:2ACM"
FT STRAND 1099..1107
FT /evidence="ECO:0007829|PDB:2ACM"
FT TURN 1109..1111
FT /evidence="ECO:0007829|PDB:2ACM"
FT HELIX 1114..1132
FT /evidence="ECO:0007829|PDB:2ACM"
FT STRAND 1136..1142
FT /evidence="ECO:0007829|PDB:2ACM"
SQ SEQUENCE 1255 AA; 122102 MW; 5E28DFC4C20D9A82 CRC64;
MTPGTQSPFF LLLLLTVLTV VTGSGHASST PGGEKETSAT QRSSVPSSTE KNAVSMTSSV
LSSHSPGSGS STTQGQDVTL APATEPASGS AATWGQDVTS VPVTRPALGS TTPPAHDVTS
APDNKPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDNRPALGS TAPPVHNVTS
ASGSASGSAS TLVHNGTSAR ATTTPASKST PFSIPSHHSD TPTTLASHST KTDASSTHHS
SVPPLTSSNH STSPQLSTGV SFFFLSFHIS NLQFNSSLED PSTDYYQELQ RDISEMFLQI
YKQGGFLGLS NIKFRPGSVV VQLTLAFREG TINVHDVETQ FNQYKTEAAS RYNLTISDVS
VSDVPFPFSA QSGAGVPGWG IALLVLVCVL VALAIVYLIA LAVCQCRRKN YGQLDIFPAR
DTYHPMSEYP TYHTHGRYVP PSSTDRSPYE KVSAGNGGSS LSYTNPAVAA TSANL
