MUC1_MOUSE
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 25-MAY-2022, entry version 146.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q02496; 16 sites.
DR iPTMnet; Q02496; -.
DR PhosphoSitePlus; Q02496; -.
DR MaxQB; Q02496; -.
DR PaxDb; Q02496; -.
DR PRIDE; Q02496; -.
DR ProteomicsDB; 287523; -.
DR DNASU; 17829; -.
DR GeneID; 17829; -.
DR KEGG; mmu:17829; -.
DR UCSC; uc008pyh.2; mouse.
DR CTD; 4582; -.
DR MGI; MGI:97231; Muc1.
DR eggNOG; ENOG502S4SC; Eukaryota.
DR InParanoid; Q02496; -.
DR OrthoDB; 945460at2759; -.
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 72 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; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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 GO; GO:0090240; P:positive regulation of histone H4 acetylation; ISO:MGI.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; ISO:MGI.
DR GO; GO:0043618; P:regulation of transcription from RNA polymerase II promoter in response to stress; ISO:MGI.
DR Gene3D; 6.10.140.600; -; 1.
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 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
