MUC1_MESAU
ID MUC1_MESAU Reviewed; 676 AA.
AC Q60528;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=Mucin-1;
DE Short=MUC-1;
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;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Tracheal epithelium;
RX PubMed=8703480; DOI=10.1165/ajrcmb.15.2.8703480;
RA Park H., Hyun S.W., Kim K.C.;
RT "Expression of MUC1 mucin gene by hamster tracheal surface epithelial cells
RT in primary culture.";
RL Am. J. Respir. Cell Mol. Biol. 15:237-244(1996).
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 (By
CC similarity). {ECO:0000250}.
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. Promotes tumor progression. Regulates P53-mediated
CC transcription and determines cell fate in the genotoxic stress
CC response. Binds, together with KLF4, the PE21 promoter element of P53
CC and represses P53 activity (By similarity). {ECO:0000250}.
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). {ECO:0000250}.
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.
CC -!- PTM: Probably both N- and O-glycosylated (in repeat 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-651 increases binding to beta-catenin/CTNNB1.
CC GSK3B-mediated phosphorylation on Ser-649 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; U36918; AAB53965.1; -; mRNA.
DR RefSeq; NP_001268584.1; NM_001281655.1.
DR AlphaFoldDB; Q60528; -.
DR STRING; 10036.XP_005080218.1; -.
DR GeneID; 101835702; -.
DR CTD; 4582; -.
DR eggNOG; ENOG502S4SC; Eukaryota.
DR OrthoDB; 945460at2759; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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 2: Evidence at transcript 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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..676
FT /note="Mucin-1"
FT /id="PRO_0000019279"
FT CHAIN 26..520
FT /note="Mucin-1 subunit alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000317450"
FT CHAIN 521..676
FT /note="Mucin-1 subunit beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000317451"
FT TOPO_DOM 26..582
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 583..603
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..676
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 40..59
FT /note="1"
FT REPEAT 60..79
FT /note="2"
FT REPEAT 80..99
FT /note="3"
FT REPEAT 100..119
FT /note="4"
FT REPEAT 120..139
FT /note="5"
FT REPEAT 140..159
FT /note="6"
FT REPEAT 160..179
FT /note="7"
FT REPEAT 180..199
FT /note="8"
FT REPEAT 200..219
FT /note="9"
FT REPEAT 220..239
FT /note="10"
FT REPEAT 240..259
FT /note="11"
FT REPEAT 260..279
FT /note="12"
FT REPEAT 280..299
FT /note="13"
FT DOMAIN 463..570
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT REGION 25..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 40..314
FT /note="13 X approximate tandem repeats of P-V-H-S-G-S-S-A-
FT P-P-T-S-S-A-V-N-S-A-T-T"
FT REGION 404..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 614..650
FT /note="Interaction with P53"
FT /evidence="ECO:0000250"
FT REGION 636..659
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 645..652
FT /note="Required for interaction with GSK3B"
FT /evidence="ECO:0000250"
FT REGION 655..662
FT /note="Required for interaction with beta- and gamma-
FT catenins"
FT /evidence="ECO:0000250"
FT MOTIF 625..628
FT /note="Interaction with GRB2"
FT /evidence="ECO:0000250"
FT MOTIF 651..654
FT /note="Interaction with SRC and ESR1"
FT /evidence="ECO:0000250"
FT MOTIF 664..667
FT /note="Required for interaction with AP1S2"
FT /evidence="ECO:0000250"
FT SITE 520..521
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT MOD_RES 625
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 634
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 640
FT /note="Phosphotyrosine; by PDGFR"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 646
FT /note="Phosphothreonine; by PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 649
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 651
FT /note="Phosphotyrosine; by CSK, EGFR and SRC"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT MOD_RES 664
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P15941"
FT LIPID 606
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 608
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 43
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 45
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 46
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 50
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 51
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 58
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 400
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 536
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 676 AA; 67617 MW; 95F479B6EC5C3884 CRC64;
MTPGIRAPFL LTLLLALVTD PNSVALSQDT SSSSTLNTTP VHSGSSAPAT SSAVDSATTP
GHSGSSAPPT SSAVNSATTP GHSGSSAPPT SSAVNSATTP VHSGSSAPVT SSAVNSATTP
VHSGSSAPPT SSAVNSATTP VHSGSSAPVT SSAVNSATTP VHSGSSAPVT SSAVDSATTP
VHSGSSAPPT SSAVNSATTP VHSGSSAPVT SSAVNSATTP VHSGSSAPVT SSAVNSATTP
VHSGSSAPPT SSVVNSATTP VHSGSSAPPT SSAVNLATTP VHSGSSTPAT NSTTDSATTP
VPPGSSMQTT EAISGSANTP IHNGSLVPTT SSALVPTTSA AHSGASAMTN SSESDLATTP
IDSGTSISTT KAPATTPVHN GSLVPTTSSV LGSATTLIHN DTSTMATTTP VGNGTQSSVP
SRHPVTPTPP AVSSNSTIAL STYYSTALSP AFSSHAAPQV SVGVSFFLLS FHIWNHQFNS
SLEDPSSNYY QELKRNVSGL FLQVFSRAFL GISTIEFRSG SVVVDSTVIF REGAVNASEV
KSQLLQHEQE AEEYNLAISK INVGEMQFPS SAQSWPGVPG WGIALLVLVC ILVALAIVYL
IALAVCQCRR KNYGQLDIFP IQDSYHPMSE YPTYHTHGRY VPPGSTKRSP YEEVSAGNGS
SLSYTNPVVA TTSANL
