ID   MUC1_MOUSE              Reviewed;         630 AA.
AC   Q02496;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 2.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Mucin-1;
DE            Short=MUC-1;
DE   AltName: Full=Episialin;
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=Muc-1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1714452; DOI=10.1016/s0021-9258(18)98592-3;
RA   Spicer A.P., Parry G., Patton S., Gendler S.J.;
RT   "Molecular cloning and analysis of the mouse homologue of the tumor-
RT   associated mucin, MUC1, reveals conservation of potential O-glycosylation
RT   sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-
RT   like polymorphism.";
RL   J. Biol. Chem. 266:15099-15109(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=1958179; DOI=10.1016/s0006-291x(05)81390-7;
RA   Vos H.L., Devries Y., Hilkens J.;
RT   "The mouse episialin (Muc1) gene and its promoter: rapid evolution of the
RT   repetitive domain in the protein.";
RL   Biochem. Biophys. Res. Commun. 181:121-130(1991).
RN   [3]
RP   INTERACTION WITH CAMPYLOBACTER JEJUNI AND P53, INDUCTION, AND
RP   PHOSPHORYLATION.
RX   PubMed=17641781; DOI=10.1172/jci26705;
RA   McAuley J.L., Linden S.K., Png C.W., King R.M., Pennington H.L.,
RA   Gendler S.J., Florin T.H., Hill G.R., Korolik V., McGuckin M.A.;
RT   "MUC1 cell surface mucin is a critical element of the mucosal barrier to
RT   infection.";
RL   J. Clin. Invest. 117:2313-2324(2007).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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-kappaB
CC       pathways. In activated T-cells, influences directly or indirectly the
CC       Ras/MAPK pathway. Regulates P53-mediated transcription and determines
CC       cell fate in the genotoxic stress response. Binds, together with KLF4,
CC       the PE21 promoter element of P53 and represses P53 activity.
CC   -!- SUBUNIT: The alpha subunit forms a tight, non-covalent heterodimeric
CC       complex with the proteolytically-released beta-subunit. Binds directly
CC       the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in
CC       RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several
CC       proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain
CC       of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-
CC       catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction
CC       with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2,
CC       ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2
CC       and, 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 (By
CC       similarity). C.jejeuni adheres to gastric epithelial MUC1 and modulates
CC       its transcription. {ECO:0000250, ECO:0000269|PubMed:17641781}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane; Single-pass type I membrane
CC       protein. Note=Exclusively located in the apical domain of the plasma
CC       membrane of highly polarized epithelial cells. After endocytosis,
CC       internalized and recycled to the cell membrane. Located to microvilli
CC       and to the tips of long filopodial protusions (By similarity).
CC       {ECO:0000250}.
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 (By similarity). Some transportation to the nucleus when
CC       infected with C.jejeuni. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in a variety of epithelial tissues.
CC   -!- PTM: Probably both N- and extensively O-glycosylated (in repeat
CC       region).
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. Ectodomain shedding is mediated by ADAM17 in uterine epithelial
CC       cells (By similarity). {ECO:0000250}.
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:0000250}.
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. Csk- or Src- or EGFR-mediated
CC       phosphorylation on Tyr-604 increases binding to beta-catenin/CTNNB1.
CC       GSK3B-mediated phosphorylation on Ser-602 decreases this interaction
CC       but restores the formation of the beta-cadherin/E-cadherin complex. On
CC       T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated
CC       phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1
CC       (By similarity). {ECO:0000250}.
CC   -!- CAUTION: O-glycosylation sites are annotated in first sequence repeat
CC       only. Residues at similar position are probably glycosylated in all
CC       repeats. {ECO:0000305}.
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DR   EMBL; M65132; AAA39755.1; -; Genomic_DNA.
DR   EMBL; M64928; AAA39755.1; JOINED; Genomic_DNA.
DR   EMBL; M84683; AAA39756.1; -; mRNA.
DR   EMBL; U16175; AAA98538.1; -; Genomic_DNA.
DR   EMBL; M77226; AAA39754.1; -; Genomic_DNA.
DR   PIR; A39344; A39344.
DR   PIR; I52257; I52257.
DR   RefSeq; NP_038633.1; NM_013605.2.
DR   AlphaFoldDB; Q02496; -.
DR   SMR; Q02496; -.
DR   BioGRID; 201606; 1.
DR   CORUM; Q02496; -.
DR   STRING; 10090.ENSMUSP00000041963; -.
DR   GlyCosmos; Q02496; 16 sites, No reported glycans.
DR   GlyGen; Q02496; 16 sites.
DR   iPTMnet; Q02496; -.
DR   PhosphoSitePlus; Q02496; -.
DR   MaxQB; Q02496; -.
DR   PaxDb; 10090-ENSMUSP00000041963; -.
DR   ProteomicsDB; 287523; -.
DR   DNASU; 17829; -.
DR   GeneID; 17829; -.
DR   KEGG; mmu:17829; -.
DR   UCSC; uc008pyh.2; mouse.
DR   AGR; MGI:97231; -.
DR   CTD; 4582; -.
DR   MGI; MGI:97231; Muc1.
DR   eggNOG; ENOG502S4SC; Eukaryota.
DR   InParanoid; Q02496; -.
DR   OrthoDB; 5363311at2759; -.
DR   PhylomeDB; Q02496; -.
DR   TreeFam; TF336301; -.
DR   Reactome; R-MMU-913709; O-linked glycosylation of mucins.
DR   Reactome; R-MMU-977068; Termination of O-glycan biosynthesis.
DR   BioGRID-ORCS; 17829; 3 hits in 77 CRISPR screens.
DR   ChiTaRS; Muc1; mouse.
DR   PRO; PR:Q02496; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q02496; Protein.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0000785; C:chromatin; ISO:MGI.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0002039; F:p53 binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0003712; F:transcription coregulator activity; ISO:MGI.
DR   GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISO:MGI.
DR   GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; ISO:MGI.
DR   GO; GO:0051179; P:localization; ISO:MGI.
DR   GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISO:MGI.
DR   GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:MGI.
DR   GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:MGI.
DR   Gene3D; 6.10.140.600; -; 1.
DR   InterPro; IPR000082; SEA_dom.
DR   InterPro; IPR036364; SEA_dom_sf.
DR   PANTHER; PTHR10006:SF19; MUCIN-1; 1.
DR   PANTHER; PTHR10006; MUCIN-1-RELATED; 1.
DR   Pfam; PF01390; SEA; 1.
DR   SMART; SM00200; SEA; 1.
DR   SUPFAM; SSF82671; SEA domain; 1.
DR   PROSITE; PS50024; SEA; 1.
PE   1: Evidence at protein level;
KW   Autocatalytic cleavage; Cell membrane; Cytoplasm; Glycoprotein;
KW   Lipoprotein; Membrane; Nucleus; Palmitate; Phosphoprotein;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..20
FT   CHAIN           21..630
FT                   /note="Mucin-1"
FT                   /id="PRO_0000019280"
FT   CHAIN           21..473
FT                   /note="Mucin-1 subunit alpha"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000317452"
FT   CHAIN           474..630
FT                   /note="Mucin-1 subunit beta"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000317453"
FT   TOPO_DOM        21..535
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        536..556
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        557..630
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          42..61
FT                   /note="1"
FT   REPEAT          62..81
FT                   /note="2"
FT   REPEAT          82..101
FT                   /note="3"
FT   REPEAT          102..122
FT                   /note="4; approximate"
FT   REPEAT          123..143
FT                   /note="5; approximate"
FT   REPEAT          144..164
FT                   /note="6; approximate"
FT   REPEAT          165..184
FT                   /note="7"
FT   REPEAT          185..204
FT                   /note="8"
FT   REPEAT          205..225
FT                   /note="9; approximate"
FT   REPEAT          226..246
FT                   /note="10; approximate"
FT   REPEAT          247..256
FT                   /note="11"
FT   REPEAT          257..286
FT                   /note="12"
FT   REPEAT          287..306
FT                   /note="13"
FT   REPEAT          307..326
FT                   /note="14"
FT   REPEAT          327..346
FT                   /note="15"
FT   REPEAT          347..366
FT                   /note="16"
FT   DOMAIN          416..521
FT                   /note="SEA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT   REGION          30..305
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          42..366
FT                   /note="16 X 20 AA approximate tandem repeats"
FT   REGION          567..603
FT                   /note="Interaction with P53"
FT                   /evidence="ECO:0000269|PubMed:17641781"
FT   REGION          589..615
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          598..605
FT                   /note="Required for interaction with GSK3B"
FT                   /evidence="ECO:0000250"
FT   REGION          608..616
FT                   /note="Required for interaction with beta- and gamma-
FT                   catenins"
FT                   /evidence="ECO:0000250"
FT   MOTIF           578..581
FT                   /note="Interaction with GRB2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           604..607
FT                   /note="Interaction with SRC and ESR1"
FT                   /evidence="ECO:0000250"
FT   MOTIF           618..621
FT                   /note="Required for interaction with AP1S2"
FT                   /evidence="ECO:0000250"
FT   SITE            473..474
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         578
FT                   /note="Phosphotyrosine; by PDGFR"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         587
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         593
FT                   /note="Phosphotyrosine; by PDGFR"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         599
FT                   /note="Phosphothreonine; by PKC/PRKCD"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         602
FT                   /note="Phosphoserine; by GSK3-beta"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         604
FT                   /note="Phosphotyrosine; by CSK, EGFR and SRC"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   MOD_RES         618
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P15941"
FT   LIPID           559
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           561
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        43
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        44
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        45
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        46
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        50
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        51
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        53
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        57
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        275
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        335
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        432
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        449
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        508
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        120..121
FT                   /note="LS -> PL (in Ref. 1; AAA39755)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        138..139
FT                   /note="AT -> PA (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        140
FT                   /note="T -> TT (in Ref. 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        423
FT                   /note="S -> F (in Ref. 1; AAA39755)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        506
FT                   /note="D -> S (in Ref. 1; AAA39755)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        602
FT                   /note="S -> Q (in Ref. 1; AAA39755)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   630 AA;  64539 MW;  D9EC2A0815F65E8E CRC64;
     MTPGIRAPFF LLLLLASLKG FLALPSEENS VTSSQDTSSS LASTTTPVHS SNSDPATRPP
     GDSTSSPVQS STSSPATRAP EDSTSTAVLS GTSSPATTAP VNSASSPVAH GDTSSPATSL
     SKDSNSSPVV HSGTSSAATT APVDSTSSPV VHGGTSSPAT SPPGDSTSSP DHSSTSSPAT
     RAPEDSTSTA VLSGTSSPAT TAPVDSTSSP VAHDDTSSPA TSLSEDSASS PVAHGGTSSP
     ATSPLRDSTS SPVHSSASIQ NIKTTSDLAS TPDHNGTSVT TTSSALGSAT SPDHSGTSTT
     TNSSESVLAT TPVYSSMPFS TTKVTSGSAI IPDHNGSSVL PTSSVLGSAT SLVYNTSAIA
     TTPVSNGTQP SVPSQYPVSP TMATTSSHST IASSSYYSTV PFSTFSSNSS PQLSVGVSFF
     FLSFYIQNHP FNSSLEDPSS NYYQELKRNI SGLFLQIFNG DFLGISSIKF RSGSVVVEST
     VVFREGTFSA SDVKSQLIQH KKEADDYNLT ISEVKVNEMQ FPPSAQSRPG VPGWGIALLV
     LVCILVALAI VYFLALAVCQ CRRKSYGQLD IFPTQDTYHP MSEYPTYHTH GRYVPPGSTK
     RSPYEEVSAG NGSSSLSYTN PAVVTTSANL
//